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.