BACKGROUND Babesiosis is endemic in selected areas in North America. Babesia infection is commonly associated with anemia, thrombocytopenia, hyponatremia and elevated liver enzymes. Autoimmune hemolytic anemia (AIHA) is known to be caused by parasitic and viral infections but has not been well characterized. METHODS We describe two cases diagnosed with babesiosis triggering severe AIHA. One case had history of splenectomy, and the other was an elderly patient. Older, immunocompromised and asplenic patients may be particularly at risk for post-babesiosis AIHA (PB-AIHA). CONCLUSIONS The pathogenesis for conventional AIHA and PB-AIHA appears to be different, since splenectomy is a treatment for conventional AIHA, whereas PB-AIHA is seen more often in asplenic patients. Further investigation into this intriguing mechanism of host immune response to babesiosis may help to elucidate the overall mechanism of infection- triggered AIHA.