Drotrecogin alfa (activated) is a drug licensed for the treatment of severe sepsis. We describe the care of a 61-year-old man who developed multi-organ failure secondary to severe falciparum malaria infection with parasitaemia levels of 40%. Included in his care were an exchange blood transfusion and an infusion of Drotrecogin alfa (activated). Within hours of starting the infusion of Drotrecogin alfa (activated), the patient's clinical condition stopped deteriorating. Steady improvement followed with weaning from ventilatory assistance on day 14 post admission. The patient made a full recovery and was discharged home following rehabilitation. The indications for Drotrecogin alfa (activated) and the appropriateness of its use in severe malaria with multi-organ failure are discussed. Drotrecogin alfa (activated) may be a useful treatment in patients with multi-organ failure resulting from severe malaria.