Investigation of an unexplained fever (PUO)
A careful, step-by-step specialist work-up to find the cause of a fever that has lasted some time without an obvious explanation.
✓ Medically reviewed by a GMC-registered consultant · last reviewed September 2026 · next review September 2027 · how we review
In short
- PUO is a long-lasting fever without an obvious cause, not a diagnosis — it is the start of a careful search.
- There is no single test: a specialist works through history, examination and staged tests guided by the clues found.
- Causes span infection, inflammation, cancer and a mixed group, and the work-up is tailored to your age, travel and health.
- Finding the cause can take time and patience; a methodical approach is safer than one 'catch-all' scan or a blind course of treatment.
A plain-English summary. The detail — including risks and recovery — is below.
At a glance
A general guide. Your specialist will give you advice for your situation.
Works methodically towards the true cause rather than guessing
A blind 'whole-body scan to find everything' is the wrong approach without the guiding history and examination, and can mislead.
After the history and examination, the specialist explains the likely groups of causes and which first tests they recommend and why.
A named specialist coordinating the work-up and explaining each step.
After the history and examination, the specialist explains the likely groups of causes and which first tests they...
Blood, urine and culture results come back over several days and are reviewed together, often pointing to the...
Scans and specific tests are arranged based on the clues. Some results are quick; others, such as certain...
A sample may be taken from a suspicious area; results from the laboratory usually take several days and can give a...
What is an investigation of an unexplained fever (PUO)?
Pyrexia of unknown origin (PUO) is the medical term for a fever that has lasted a while, usually weeks, and has not been explained despite some initial checks. It is not a diagnosis in itself: it is a starting point for finding out what is causing the temperature.
There is no single test for PUO. Instead, a specialist builds the picture step by step, beginning with a detailed history and a thorough examination, then choosing tests guided by the clues these reveal. Causes fall into broad groups: infections, inflammatory or autoimmune conditions, cancers, and a mixed 'other' group. The likely causes differ depending on age, travel, medicines and whether the immune system is weakened.
The aim is to reach a clear, correct diagnosis without rushing into unnecessary or risky tests. Sometimes the answer comes quickly; sometimes it takes time, repeated reviews and a degree of patience, and occasionally the fever settles before a cause is found.
A good work-up is methodical and tailored to you. It avoids the trap of one 'catch-all' scan or treatment, because the right next test depends on what has been found so far.
Types, options & approaches
There may be different ways to do this. The right approach depends on the clinical question and your circumstances.
Broad groups of causes
| Group | Examples |
|---|---|
| Infection | Hidden abscess, TB, endocarditis, viral illness |
| Inflammatory / autoimmune | Vasculitis, connective-tissue disease |
| Cancer | Lymphoma, some solid tumours |
| Other / mixed | Drug fever, clots, thyroid problems |
The mix differs by age, travel and immune status, and in many people a cause is found through a step-by-step approach; in some, the fever settles unexplained.
Preparing for your test
- Keep a simple diary of your temperatures, when they rise and fall, and any other symptoms, to share with the specialist.
- Write down all recent travel, including dates and places, as some causes are travel-related.
- List every medicine and supplement, including recent courses, as some medicines cause fever.
- Note any contact with animals, ticks, unwell people, or unusual foods, and your occupation and hobbies.
- Bring details of past illnesses, operations, vaccinations and any previous test results.
- Mention anything that weakens the immune system, such as HIV, certain medicines or recent chemotherapy.
- Be ready for the work-up to take time and several appointments, rather than one quick answer.
What happens
The specialist starts by taking a very detailed history and examining you carefully, often more thoroughly than in a routine appointment, because small clues guide everything that follows. This first step often narrows the possibilities considerably.
From there, tests are chosen in a staged way. First-line blood, urine and culture tests look for infection and inflammation, with targeted tests for specific infections or autoimmune conditions added as clues emerge. Imaging, such as ultrasound, CT, MRI or sometimes a whole-body PET-CT, is used to look for a hidden source.
If a particular area stands out, a sample (biopsy) may be taken and examined to reach a precise diagnosis. Throughout, results are reviewed together and the plan is adjusted, rather than every test being done at once.
Sometimes the work-up involves a short hospital stay so that closely linked tests can be done quickly, especially if you are unwell. In many people a cause is found; in some, the fever settles before a diagnosis is reached, and careful review continues.
Is this test right for me?
A good consultation should explore whether it's the right choice for you now — including reasons to wait or consider something else.
May not be suitable if…
- A blind 'whole-body scan to find everything' is the wrong approach without the guiding history and examination, and can mislead.
- Starting treatment (such as antibiotics or steroids) before a diagnosis can mask the cause and is generally avoided unless you are seriously unwell.
- A short-lived fever that has not yet lasted long enough does not usually need the full PUO work-up.
- Over-testing for rare conditions that do not fit the clinical picture adds risk without benefit.
Delay or rearrange if…
- You are acutely and severely unwell and need urgent, same-day assessment rather than a staged outpatient work-up.
- A recent course of medicine could itself be causing the fever and may be reviewed first.
- Key earlier results are missing and would change which test comes next.
- Pregnancy or other circumstances affect which tests are safe and need planning.
Alternatives to discuss
- A period of careful watchful waiting with repeated review, as some fevers settle and new clues emerge
- Stopping a suspected medicine to see if the fever resolves (drug fever)
- Referral to a different specialty (such as rheumatology or haematology) if clues point there
- Stepwise outpatient testing rather than admission, where you are well enough
- A second opinion if the work-up stalls
Before you decide
Use this as a shared-decision checklist. The aim is not just “can this be done?”, but whether it is right for you, now, with the risks and alternatives clearly understood.
What matters most to me?
Think about symptoms, daily life, work, caring responsibilities, sport, fertility, travel, appearance and anxiety — the right choice depends on your priorities, not just the medical facts.
What are all my options?
Ask about waiting, monitoring, medicines, rehabilitation, a smaller or larger procedure, a different test, NHS referral, or a second opinion where that would help.
What would make me pause?
Active infection, pregnancy, unstable medical problems, smoking, medicines that increase bleeding, poor support at home, or feeling pressured are all reasons to slow down and get tailored advice.
What happens if I do nothing today?
For some problems, waiting is safe; for others, delay can make treatment harder. A good consultation should explain the trade-off in plain English.
Benefits
- Works methodically towards the true cause rather than guessing
- Avoids unnecessary or risky tests by following the clues
- Can uncover treatable infections, inflammatory conditions or cancers early
- Brings together different specialists' input where needed
- Reduces the chance of a wrong diagnosis from a single misleading test
- Provides reassurance and a clear plan even when answers take time
Risks & complications
- Discomfort and bruising from repeated blood tests
- Uncertainty and worry while waiting for a diagnosis
- A work-up that takes time and several appointments
- Incidental findings on scans that need further tests but turn out not to be the cause
- Tests that come back normal or inconclusive, requiring repetition
- Radiation exposure from some imaging, weighed against the value of the information
- Side effects from contrast used in some scans
- Complications from a biopsy, such as bleeding or infection
- A reaction to imaging contrast
- The cause remaining undiagnosed despite a thorough work-up
The main risk in PUO is not the individual tests but two opposite traps: doing a blind 'catch-all' scan or starting treatment before a diagnosis, and, on the other hand, over-testing for rare conditions that do not fit. A good specialist explains what each test is for, what a normal or abnormal result would change, and why some patience is often safer than rushing. Ask what the next step depends on.
Published figures to discuss
How often a cause is found, and what that cause turns out to be, varies widely between studies and populations, depending on age, travel, immune status and how far the work-up goes. A meaningful proportion of fevers settle without a definite diagnosis. Because these figures differ so much by setting, we have not quoted precise percentages here; the value of the work-up lies in a careful, staged approach rather than in any single test's accuracy.
| Figure | Reported range | How to interpret it | Source / confidence |
|---|---|---|---|
| No cause found despite investigation | Meaningful minority in many series | Some prolonged fevers settle without a firm diagnosis; follow-up is still important to catch evolving disease. | Guide sourcesClinical context |
| Serious cause initially hidden | Depends on age, immune status and symptoms | Infection, inflammatory disease, cancer and drug fever can all present non-specifically. | Pyrexia of unknown origin — review (PMC)ncbi.nlm.nih.govSource-linked context |
| Harm from repeated empirical antibiotics | Avoidable | Antibiotics without a target can mask cultures, cause side effects and delay the correct diagnosis. | Guide sourcesClinical context |
| High-risk fever red flags | Urgent if present | Confusion, low blood pressure, breathlessness, rash, neck stiffness, immunosuppression or recent tropical travel changes the urgency. | Pyrexia of unknown origin — review (PMC)ncbi.nlm.nih.govSource-linked context |
These are literature figures, not a personalised prediction. Your own risks and likely benefits depend on your circumstances, your health, and how your care is carried out and followed up.
What happens afterwards
There is no single procedure to recover from. 'Afterwards' means how the picture builds up over time, when you get answers, and what each result changes about your care.
- Several rounds of blood tests and a series of appointments
- A gradual build-up of information rather than one quick answer
- Periods of waiting for results, which can feel frustrating
- Being reviewed again if early tests are normal or the fever continues
Aftercare
- Keep recording your temperatures and symptoms, as patterns help the diagnosis.
- Attend all the tests and reviews arranged, even if you feel a little better.
- Take any treatment as prescribed, and report whether your fever responds to it.
- Tell the team about any new symptom, however minor, as it may be the missing clue.
- Keep your medicines list up to date, as some medicines themselves cause fever.
- Ask who to contact if you become more unwell between appointments.
- Be prepared for the answer to take time, and ask what each result will change.
- A temperature and symptom diary
- A written list of travel, animal and contact history
- An up-to-date list of all medicines and supplements
- Previous test results and hospital letters gathered
- A note of who to contact if you get worse
- Questions ready about what each test is for and what it will change
⚠ Get urgent help if…
- Becoming rapidly more unwell, very drowsy or confused — seek urgent medical help.
- Breathlessness, chest pain, or a fast heartbeat that is new or worsening.
- A spreading rash, especially one that does not fade under pressure — seek urgent help.
- A stiff neck with fever and dislike of bright light.
- Severe headache, fainting, or a fever above 40°C that will not come down.
- Heavy night sweats with marked weight loss, which should be reported promptly.
Who to contact: your clinician, clinic or test provider first (keep their number to hand). For urgent advice when you can't reach them, call NHS 111. In an emergency, call 999.
General guidance — it doesn't replace the specific advice your specialist gives you.
Results & realistic expectations
There is no single 'result' in a PUO work-up. Instead, each test adds to the picture: some rule conditions out, some point towards a group of causes, and occasionally one provides the answer. A diagnosis is usually reached by piecing these together over time.
Normal tests are not a failure — they narrow the search and can be reassuring. Importantly, even a thorough work-up cannot always find a cause, and in a proportion of people the fever settles on its own without a definite diagnosis. Your specialist will explain what has been found, what has been excluded and what the sensible next step is.
Findings from a PUO work-up reflect the situation at the time. A normal scan or test does not guarantee nothing will appear later, which is why review over time is part of the approach. If a cause is found and treated, follow-up checks whether the fever and any underlying condition respond. If no cause is found and the fever settles, you may simply be reviewed, with the option to investigate again if symptoms return.
Related tests, treatments or support
PUO investigation routinely includes tests for infections that can cause prolonged fever, such as HIV, tuberculosis and hepatitis, so these guides are closely related. Depending on the clues, it may also bring in rheumatology, haematology or oncology input. Imaging and biopsy are often combined to pin down a source.
Follow-up & long-term care
Follow-up in PUO is built into the process. Results are reviewed together, the plan is adjusted as clues emerge, and you are seen again whether a cause is found or not. If a diagnosis is made, follow-up monitors the response to treatment. If the fever settles unexplained, you are usually reviewed, with clear advice on when to seek help if it returns.
- Continue a temperature and symptom diary until you are advised to stop.
- Attend review appointments even if early tests are normal.
- Report any new symptom promptly, as it may point to the cause.
- If a cause is found and treated, keep follow-up checks of your response.
- Seek review again if the fever returns after settling.
Repeat, follow-on and what comes next
- Normal or inconclusive tests are common and often need repeating as the picture develops.
- The plan is deliberately adjusted as clues emerge, rather than fixed at the start.
- Some fevers settle before a cause is found, and review continues.
- If symptoms return after settling, investigation may sensibly start again.
Ask what happens if the result is unclear or needs repeating, and what is included if further tests or follow-up are needed.
What good aftercare looks like
- A named specialist coordinating the work-up and explaining each step.
- A clear plan for which test comes next and what each result would change.
- Honest discussion that a cause is not always found, and what happens then.
- Continued review over time, with a route to seek help if you worsen.
- Joined-up input from other specialties when the clues point that way.
What affects the cost
Costs vary a great deal between people and providers, and we don't publish prices. What matters is understanding what drives the cost and making sure your quote is complete. The main things that affect it:
- How many and which tests are needed, which depends on the clues found
- Imaging used (ultrasound, CT, MRI or PET-CT) and whether contrast is needed
- Specialist consultations and how many reviews are required
- Any biopsy and laboratory analysis
- Whether some tests need a short hospital stay
- Input from more than one specialty where relevant
- Which initial tests and consultations are included
- How additional tests, scans or biopsies are charged as the work-up develops
- Whether reviews to interpret results are included
- Whether a hospital stay would be covered if closely linked tests are needed
- How results are communicated and who coordinates your care
- What happens if no cause is found and ongoing review is needed
On the NHS? Investigation of an unexplained fever is available on the NHS, usually through infectious-diseases or general-medicine specialists; private routes may be used for speed, choice or a second opinion.
You're entitled to your total cost in writing — including reports, follow-up and what happens if the result is inconclusive — before you decide.
Consent traps and marketing red flags
These are not small details. They are often where patients lose choice, time to reflect, or realistic expectations.
Consent traps
- Agreeing to a 'catch-all' scan without understanding what it can and cannot show.
- Not being told that a cause is not always found despite thorough investigation.
- Starting treatment before diagnosis without explaining how it may mask the cause.
- No clear plan for who coordinates care when several specialists are involved.
- Not understanding what each test is for or what a result will change.
Marketing red flags
- Promising a quick diagnosis from a single premium scan or blood panel.
- Offering broad 'fever screens' without a guiding history and examination.
- Implying every fever has a findable cause if you pay for enough tests.
- Starting treatment privately before a diagnosis to 'cover all bases'.
Choosing a specialist safely
- Check the specialist is on the GMC Specialist Register for this area.
- Make sure they work at a CQC-registered service, and look for membership of the relevant Royal College or professional body.
- You're entitled to time to consider and to have your questions answered before you agree — the specialist who looks after you should explain it, not a salesperson.
- Be wary of pressure: time-limited offers or deposits taken before you've had time to think are red flags, not bargains.
- You're entitled to your total cost in writing — including any follow-up — before you decide.
Questions to ask your medical professional
Take this to your consultation. A good specialist will welcome every one of these.
- Which groups of causes are you most considering for me, and why?
- What is each test for, and what would a normal or abnormal result change?
- Is it safer to wait and review, or to do more tests now?
- Should I be tested for infections such as HIV, TB or hepatitis as part of this?
- Who is coordinating my care if several specialists are involved?
- What should I do, and who should I contact, if I get more unwell?
- Are you on the GMC Specialist Register for this area, and which Royal College or professional body are you a member of?
- Will you be the specialist who carries out my test, and who looks after me afterwards?
- What are the risks for someone like me, and how often do your own patients have a problem or need it repeated or redone?
- What does a realistic result look like — and what can this test not achieve?
- What are my options, including waiting, doing nothing for now, or choosing a different approach?
- Can I have written information, results and aftercare instructions in a format I can use, including any accessibility or communication support I need?
- What is the total cost in writing, including any follow-ups, and how much time do I have to decide?
Frequently asked questions
Why is there no single test for my fever?
How long will it take to find the cause?
Will I need to stay in hospital?
What if no cause is ever found?
Is a whole-body scan the best way to find the cause?
Can this be investigated on the NHS?
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How we made this page
Medically reviewed by a GMC-registered consultant. Written in plain English, checked against NHS, NICE, GMC and relevant Royal College / specialist-society guidance, and kept under review. No clinic paid to appear on this page, and we publish no pricing. This is general information to help you prepare — it is not a substitute for advice from your own clinician. How we review our guides →
Source hierarchy: UK regulator and NHS/NICE guidance first, then relevant Royal College or specialist-society guidance, then peer-reviewed evidence for procedure-specific figures where available.
Sources & standards: Patient.info (professional) — Pyrexia of unknown origin Pyrexia of unknown origin — review (PMC) PUO: causes, investigation and management — PubMed FDG-PET/CT in PUO — review (PMC) NHS — High temperature (fever) in adults
Reviews reflect patients' experience of care, not clinical outcomes. For procedure volumes and outcome data see PHIN.
Last medically reviewed 2026-09-21. Spotted something wrong or out of date? Report an error in this guide.
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