Autoimmune manifestations have long been perceived as paradoxical in patients with primary immune deficiencies (PID). However, a defect in the mechanisms of control of self-reactive B and T cells may favour these manifestations. Three PID are defined by the occurrence of autoimmune manifestations: APECED (Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy), autoimmune lymphoproliferative syndrome (ALPS) and IPEX syndrome (immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome). In these conditions, organ specific autoimmune diseases such as type 1 diabetes mellitus or Hashimoto's thyroiditis are prominently encountered. Several other PID such as common variable immunodeficiency (CVID), Good syndrome and hyper-IgM syndrome are associated with a wide variety of autoimmune manifestations, mainly autoimmune cytopenias. Thus, autoimmune manifestations have been reported in 22% of patients with CVID, increasing to 50% in the subgroup of patients with systemic granulomatosis. Complement deficiencies involving components of the classical pathway are associated with systemic lupus erythematosus (SLE). Homozygous C2 deficiency, which is the most frequent hereditary deficiency in complement classical pathway components, is associated with SLE in 10% of the cases. Complete C1q and C4 deficiencies are less frequent but associated with a higher prevalence of SLE.