We report the case of a 55-year-old male European who became septic after he returned from a four-week holiday to Uganda. Soon after; he was diagnosed with severe falciparum malaria and developed multi-organ failure. Due to the worsening condition of the patient, drotrecogin alfa (activated) was started, soon after which the patient's condition significantly improved. He returned home on day 36 after admission, without neurologic sequelae. Looking at those few cases of severe forms of malaria where drotrecogin alfa (activated) was successfully used, it should at least be considered for administration in patients with severe falciparum malaria with disseminated intravascular coagulation and cerebral involvement who do not respond to or deteriorate during standard treatment.