Exchange transfusion is frequently used as an adjunctive treatment of severe malaria, although the efficacy of exchange transfusion as therapy for severe malaria remains controversial. The major perceived benefit of exchange transfusion is the rapid reduction of parasite load. However, no previous report has shown the dynamic change in parasitemia shortly following an acute load reduction. We report a 20-year-female who developed cerebral malaria and 30% parasitemia after traveling to Africa. In addition to antimalarial treatment, red cell exchange (RCX) was begun emergently with an automated blood-cell separator. Parasitemia dropped from 30 to 15% immediately after the procedure but rapidly increased to 25% after 50 min. The second procedure was performed 12 h after the first procedure. Her neurologic status returned to baseline on Day 2, and she was discharged on Day 6. Rapid increases in parasitemia can be observed after mechanical load reduction following RCX.