Hepatitis C virus (HCV) is a recognized cause of significant extrahepatic disease. Induction of autoimmune hemolytic anemia (AIHA) has been reported, either during or after interferon (IFN) treatment of HCV infection. We herein report a 56-year-old patient with HCV infection who developed severe Coombs-positive AIHA in the absence of treatment with IFN. Prednisone therapy was initiated, but intravenous immunoglobulins were added because of persistent hemolysis. Clinical course was complicated by rapid deterioration and the development of Creutzfeldt-Jakob disease. Having discarded other possible causes of AIHA, we suggest a possible association between AIHA and infection by HCV.