A 53-year-old patient, after return from a short visit to the Ivory Coast, was admitted for suspicion of hepatic encephalopathy. An acute pernicious malaria was diagnosed with associating altered consciousness, hyperthermia, icterus, hepatomegaly, and oliguria. Blood tests showed acute renal failure, pancytopenia, disseminated intravascular coagulation, metabolic acidosis and parasitaemia at 12%. An intravenous therapy with quinine and doxycycline was started without delay. One day later, an exchange blood transfusion including a erythrapheresis and plasmapheresis was undertaken. The patient's general condition improved, and he was discharged from the ICU 22 days later. The indications for exchange blood transfusion in acute pernicious malaria are discussed.