BackgroundLittle is known about the aetiology of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME); prospective studies suggest a role for premorbid mood disorder.AimsTo examine childhood and early adult adversity, ill health and physical activity as premorbid risk markers for CFS/ME by 42 years, taking psychopathology into account.MethodData were from the 1958 British birth cohort, a prospective study from birth to 42 years (n = 11 419). The outcomes were self-reported CFS/ME (n = 127) and operationally defined CFS-like illness (n = 241) at 42 years.ResultsAdjusting for psychopathology, parental physical abuse (odds ratio (OR) = 2.10, 95% CI 1.16–3.81), childhood gastrointestinal symptoms (OR = 1.58, 95% CI 1.00–2.50) and parental reports of many colds (OR = 1.65, 95% CI 1.09–2.50) were independently associated with self-reported CFS/ME. Female gender and premorbid psychopathology were the only risk markers for CFS-like illness, independent of comorbid psychopathology.ConclusionsThis confirms the importance of premorbid psychopathology in the aetiological pathways of CFS/ME, and replicates retrospective findings that childhood adversity may play a role in a minority.