The clinical importance of immunoglobulin A (IgA) deficiency in otherwise healthy individuals is not well described. We aimed to investigate the self‐reported mental and physical health and the risk of infection in IgA‐deficient blood donors compared to healthy control blood donors. Infectious events, recorded in public health registries either as prescriptions filled of any antimicrobial medicine or as hospital infections, were compared between 177 IgA‐deficient blood donors and 1770 control blood donors. A subset of the IgA‐deficient donors were further characterized by self‐reported health (Short Form‐12, n = 28) and circulating C‐reactive protein (CRP) (n = 10). IgA‐deficient individuals had lower self‐reported mental health (p = 0.01) and higher CRP (p < 0.05). A strong trend was found regarding prescription of antimicrobial medicine (hazard ratio = 1.19, p = 0.05). No association was found with hospital infections (hazard ratio = 1.02, p = 0.95) or self‐reported physical health (p = 0.86). IgA‐deficient blood donors have impaired self‐reported mental health, enhanced inflammation and possibly an increased risk of infection. Despite these findings, this study does not provide sufficient evidence to warrant specific health precautions for donors with IgA deficiency.