Summary Immune‐mediated pathways have been recognized to be of importance in the pathogenesis of chronic lymphocytic leukaemia (CLL). We assessed a broad variety of immune‐related and inflammatory conditions and subsequent CLL development among 4 million adult male veterans admitted to VA hospitals. We identified 3,680 CLL cases with up to 27 years of follow‐up. Using Poisson regression analyses restricted to immune‐related or inflammatory conditions that occurred more than one year before CLL, we estimated relative risk (RR) and 95% confidence intervals for CLL risk. Elevated CLL risk was found among individuals with prior chronic sinusitis (RR = 1·27, 1·01–1·61). Pneumonia had a borderline (RR = 1·13, 1·00–1·27) association with CLL; the risk was further elevated (RR = 1·35, 1·07–1·72) for latency <5 years. Conversely, chronic non‐rheumatic valvular heart disease was associated with 0·76‐fold (0·58–0·99) decreased risk. Herpes zoster and simplex were associated with increased (RR = 1·98, 1·40–2·79) and borderline increased (RR = 1·69, 0·96–2·98) CLL risk. There was no general association between autoimmunity and CLL; however, autoimmune haemolytic anaemia was associated with 3·86‐fold (1·93–7·74) elevated CLL risk. Individuals with chronic osteoarthritis and prostatitis had 1·14‐fold (1·03–1·25) and 1·64‐fold (1·14–2·37) elevated CLL risk. These association patterns suggest primary focus on infectious agents rather than autoantigens for future aetiologic CLL studies.