BACKGROUND Babesia species are intraerythrocytic parasitic protozoa that are endemic to the Northeast and north Midwest of the United States. Babesia microti is the most common cause of babesiosis in North America and causes a malaria-like tick-borne parasitosis. Babesia is commonly transmitted through the bite of Ixodes species ticks, often concomitantly with other tick-borne organisms such as Borrelia burgdorferi, Ehrlichia, Rickettsia rickettsii, and Anaplasma phagocytophilum. In the Midwest, Lyme disease is the most common tick-borne illness, and other organisms can sometimes be overlooked. The risk of tick-borne parasitic or bacterial infection is increased in patients after splenectomy. CASE REPORT An 89-year-old man with asplenia and multiple other comorbidities presented to the Emergency Department after a fall at home preceded by 2 to 3 days of fever and loss of appetite and 1 week of generalized weakness. The patient had thrombocytopenia, leukocytosis with neutrophilia, transaminitis, hyperbilirubinemia, and elevated creatine kinase level consistent with tick-borne illness. Laboratory testing revealed Borrelia and Babesia co-infection and other culprits were ruled out via high sensitivity PCR. Owing to the patient's asplenic status, the babesiosis was slow to resolve with appropriate treatment. After an extended 8-week treatment with azithromycin and atovaquone, the patient demonstrated clinical resolution of babesiosis with a negative blood smear. CONCLUSIONS First-line treatment with azithromycin and atovaquone is effective in treating babesiosis even in complicated patients, such as this elderly, asplenic patient. However, in cases such as this, an extended course of a first-line treatment regimen is still appropriate.