A 63-year-old women from Wisconsin presented with severe hemolytic anemia and was found to have babesiosis by red blood cell morphologic appearance and serologic testing. Despite having an intact spleen, she developed adult respiratory distress syndrome, which required prolonged mechanical ventilation. An unusually high level of parasitemia was noted and resolved completely following treatment with quinine, clindamycin, and exchange transfusion. This case illustrates that the geographic distribution and clinical severity of babesiosis may be greater than previously recognized and that reduction in parasitemia may be achieved with exchange transfusion, quinine, and clindamycin.