In Korea, Plasmodium vivax (P. vivax) is the most common agent of malaria infection. However, as travel to regions where malaria is endemic increases, so do the numbers of Plasmodium falciparum and mixed infections. P. falciparum predominates, while P. vivax is rare in west-central Africa. We report on a case of mixed malaria infection with severe hemolytic anemia caused by P. falciparum and P. vivax in a 38-year-old man after traveling to Angola. A diagnosis of P. falciparum malaria was made by microscopic examination. However, both P. vivax and P. falciparum were detected by the polymerase chain reaction (PCR). As a radical cure P. vivax, the patient was treated with mefloquine, artemether, and primaquine. Both P. falciparum and P. vivax had disappeared from peripheral blood by admission day 4, however, low grade fever and headache persisted, and his hemoglobin and hematocrit levels were depleted. A peripheral blood smear was negative for both P. vivax and P. falciparum; however, a direct anti-globulin test and anti-nuclear antibody test were positive, suggesting immune hemolytic anemia. After conservative treatment, which included a transfusion with packed red blood cells (RBC), his symptoms and signs showed improvement and laboratory findings were normalized.