Immunological phenomena have been described in infections such as infective endocarditis. However, none has been reported in the context of Babesiosis. Babesiosis is a tick-borne illness caused by the protozoa of the genus Babesia and causes infections that range from asymptomatic to severe and sometimes are fatal. This report presents the first case of ANCA/ANA positive severe babesiosis in an asplenic patient treated with repeated red blood cell exchange transfusion.