Abstract : Sickle cell disease and systemic lupus erythematosus (SLE) are two distinct chronic conditions sharing many clinical manifestations. Coexisting of these two diseases is rare, but it is important to make the diagnosis of SLE in sickle cell patients to initiate appropriate treatment and limit the risk of complications. High titers of autoantibodies have been reported in sickle cell patients as well as a higher risk of immune deficiency. These patients present a defective activation of the alternative pathway of the complement that increases the risk of infection with encapsulated bacteria and a difficulty in eliminating antigenes that could predispose to autoimmune diseases. We report three case of children with sickle cell disease. They developed symptoms initially attributed to sickle cell disease, but after investigations revealed an underlying SLE.