Infection with the tick-borne protozoa Babesia is becoming more common. Babesiosis is usually successfully treated with antibiotics but, in some cases, apheresis may also be indicated. We report two patients with babesiosis and hemolysis treated by apheresis and antibiotics. One case had traditional indications for red blood cell (RBC) exchange, and a second patient was treated with RBC exchange, and plasmapheresis for hemolysis, probably secondary to Babesia parasitemia. Case 1 involved a 44-year-old man with chronic relapsing pancreatitis who had become infected with Babesia from a unit of RBCs transfused during surgery. At 5 weeks after surgery, fever and severe hemolysis developed, along with a hemoglobin of 69 g/L; 30% of his RBCs were found to be infected with Babesia. This patient had several postoperative complications; the babesiosis was treated with clindamycin, quinine, and three RBC exchanges. Parasitemia fell to less then 1% of RBCs, but the patient died of pancreatitis. Case 2 was a 47-year-old man with a renal transplant who had been receiving immunosuppressive therapy for 8 years. He had a history of tick bites, fever, and hemolytic anemia. Analysis of a peripheral blood smear detected Babesia. He was initially treated with antibiotic therapy and two RBC exchanges. Hemolysis improved transiently but worsening parasitemia developed later, as well as an IgG RBC autoantibody. He was then treated by plasmapheresis and RBC exchange. Although his condition improved, he had a third hemolytic episode, which was treated with plasmapheresis and RBC exchange before the parasitemia and autoimmune hemolytic anemia disappeared. In conclusion, immunosuppressed or severely ill people who become infected with Babesia may benefit from RBC exchange or plasmapheresis, or both.