Causes of Fever: From Infections to Inflammation

Fever is not a disease in itself but a warning signal. In most cases, a harmless self-limiting infection is behind it, but sometimes fever is the first sign of a serious illness. To assess risk correctly, it is important to know the main causes of fever and how clinicians structure the differential diagnosis.

This guide is aimed at interested laypeople and healthcare professionals. It does not replace medical consultation but provides a structured overview from acute infections to inflammatory and malignant causes of fever.

What is a fever? Definition and thresholds

In adults, fever is usually defined as a body temperature of about 38.0 °C (100.4 °F) or higher. Normal temperature varies by person, time of day and measurement site, but typically lies between about 36.5 and 37.5 °C. Temperatures from 39.0–40.0 °C are often referred to as high fever.

Typical ranges (oral measurement):

Normal: approx. 36.5–37.5 °C
Elevated temperature: approx. 37.5–38.0 °C
Fever: from approx. 38.0 °C
High fever: from approx. 39.0 °C
Very high fever: from approx. 40.0 °C

"Fever is a symptom – the art lies in understanding what is causing it."

Fever vs. hyperthermia

In fever, the hypothalamic "set point" is actively raised – for example in response to infection. In hyperthermia (such as heat stroke or heat exhaustion), the body's heat-regulating mechanisms are overwhelmed without a changed set point. This distinction matters particularly on hot days and in older adults with comorbidities.

When is a fever dangerous? Key red flags

Most short-lived fevers in otherwise healthy adults are caused by self-limiting infections. However, there are situations in which urgent medical care is essential.

Seek emergency care or call emergency services if you notice:

Fever above 40 °C (104 °F) or rapidly worsening overall condition
Severe neck stiffness, light sensitivity, intense headache (possible meningitis)
Shortness of breath, chest pain, confusion, seizures
Cold, mottled skin, very rapid pulse, altered mental status (possible sepsis)
Fever in infants under 3 months of age
Fever in people with severely weakened immune systems (e.g., chemotherapy, high-dose steroids)

Contact a doctor if fever lasts longer than 3–5 days, keeps coming back, or is associated with weight loss, night sweats or new lymph node swelling.

A practical approach to fever differential diagnosis

Clinicians often structure the search for fever causes along three dimensions:

Duration and pattern of fever
Associated symptoms
Risk factors and exposures

1. Duration and pattern

Acute fever (hours to a few days): most often due to respiratory, urinary or gastrointestinal infections.
Persistent fever (≥ 5–7 days): may indicate autoimmune disease, inflammatory conditions or malignancy in addition to infection.
Recurrent or periodic fever: seen in some rheumatic diseases, chronic infections and hematologic malignancies.

2. Associated symptoms

Additional symptoms provide important diagnostic clues:

Fever + cough/sore throat/runny nose → respiratory infections
Fever + burning on urination/flank pain → urinary tract infection or pyelonephritis
Fever + nausea/vomiting/diarrhoea → gastrointestinal infections
Fever + rash → viral exanthems, drug reactions, autoimmune disease
Fever + severe headache, neck stiffness → possible meningitis
Fever + joint pain/swelling → rheumatic or inflammatory disease
Fever + night sweats + weight loss → "B symptoms", e.g., lymphoma or chronic infection

3. Risk factors and exposures

A careful history should include:

Recent travel (e.g., to areas with malaria or dengue)
Tick bites (e.g., Lyme disease, tick-borne encephalitis)
Contact with ill persons (household, childcare, workplace)
Animal contact, unpasteurised dairy, undercooked meat
Medications, vaccinations, recreational drug use
Chronic diseases and any form of immunosuppression

Major etiologic groups of fever

Guidance on fever of unknown origin often groups causes into four broad categories:

Infections
Noninfectious inflammatory disease (e.g., autoimmune conditions)
Malignancies
Miscellaneous (e.g., drug fever, thromboembolism, endocrine causes, heat illness)

Infections – the most common cause

Most acute febrile episodes are caused by viral or bacterial infections. Examples include upper and lower respiratory tract infections, pneumonia, urinary tract infections and skin or soft-tissue infections.

For persistent or severe fever, it is critical to recognise signs of sepsis: rapid heart rate, rapid breathing, confusion, cold or mottled skin and profound weakness. Sepsis is a medical emergency.

Noninfectious inflammatory and autoimmune diseases

If fever persists without clear evidence of infection, noninfectious inflammatory disease comes into focus. These include conditions such as systemic lupus erythematosus, vasculitis, rheumatoid arthritis, inflammatory bowel disease and rare autoinflammatory syndromes.

Certain cancers, particularly lymphomas and leukaemias, can present with fever. Typical features are B symptoms: unexplained weight loss, drenching night sweats and persistent fever.

Drug fever and other causes

Medications are an important cause of prolonged or recurrent fever. Common culprits include some antibiotics, antiepileptics and cardiovascular drugs. Drug fever typically begins days after starting a medication and improves after it is stopped.

What patients can do

For mild fever without red flags, focus on hydration, rest and monitoring. Lightweight clothing and lukewarm drinks can improve comfort.

Fever-lowering medicines such as paracetamol (acetaminophen) or ibuprofen may be helpful if used in the recommended dose. Symptomatic treatment never replaces the search for the underlying cause.