It is the hallmark symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and common in long COVID and fibromyalgia.

Typically, it begins 12–48 hours after the activity that triggers it, and lasts for days, but this is highly variable and may persist much longer.

One of the first definitions of ME/CFS, the Holmes Criteria published in 1988, does not use the term post-exertional malaise but describes prolonged fatigue after exercise as a symptom.

[4] Sensory overload,[13] emotional distress, injury, sleep deprivation, infections, and spending too long standing or sitting up are other potential triggers.

[6] The resulting symptoms are disproportionate to the triggering activity and are often debilitating, potentially rendering someone housebound or bedbound until they recover.

Pacing, a management strategy in which someone plans their activities to stay within their limits, may help avoid triggering PEM.

[26] Physical therapy for people with long COVID must be modified to avoid triggering PEM in susceptible patients.