We report our experience on rituximab-cyclophosphamide-dexamethasone (RCD) combination therapy for the treatment of autoimmune disorders in 48 patients with chronic lymphocytic leukemia (CLL). The diagnosis of autoimmune disease (AID) was autoimmune hemolytic anemia (AIHA) in 26 (54%), autoimmune thrombocytopenic purpura (AITP) in nine (18.8%), Evans syndrome in eight (16.7%), and pure red cell anemia (PRCA) in five patients (10.5%). CLL was considered progressive in 40% of subjects upon AID diagnosis. Overall, an 89.5% response rate was obtained with this combination, irrespective of the AID type. Relapse occurred in 19 patients (39.6%). The median duration of autoimmunity was 24 months, but the duration of response of autoimmunity (DR-AI) was higher for patients presenting with: (1) AID early during the CLL course (<3 years), or (2) both and pure red cell aplasia (PRCA) in five patients (10.5%) and AIHA.