Changes in blood and blood vessels are a pathological hallmark of Plasmodium falciparum infection, and are particularly intense in its deadly complication, cerebral malaria (CM). Mechanical obstruction of cerebral blood vessels by sequestration of parasitized red blood cells (pRBCs) reduces cerebral blood fow and oxy gen consumption1–3 . Anemia and loss of RBC deformability impair the perfusion of various organs4 . Severe malaria also leads to alterations of biochemical characteristics of the plasma, with depletion of plasmatic factors related with vascular health such as l-arginine5 , haptoglobin6 and angiopoietin-1 (Ang-1), a critical regulator of endothelial integrity7 . Ang-1 maintains vascular quiescence by signaling through the Tie-2 receptor8 , whereas Ang-2, stored in Weibel-Palade bodies, can be rapidly released upon endothelial activation and displace Ang-1, sensitizing the endothelium to low concentrations of infammatory cytokines such as TNF8 . Indeed, Ang-2 levels are elevated in severe malaria9 and have been associated with CM retinopathy10, and blood-retinal breakdown associated with death or sequelae in pediatric CM11. Together with coagulation disorders like platelet activa tion and thrombocytopenia12,13, these changes disturb endothelial quiescence, leading to vascular dysfunction, impaired cerebral perfusion, acidosis14 and breakdown of the blood–brain barrier (BBB)15. Whole blood transfusion is a practice already adopted in the adjuvant treatment of patients with severe malarial anemia16. In areas of high malaria endemicity, the World Health Organization (WHO) recommends blood transfusion when the hemoglobin concentration is less than 4 g/dL, this threshold is increased to 6 g/dL in case anemia is accompanied by acidosis, impaired consciousness, shock, or parasitaemia greater than 20%17,18. Recently, Ackerman and colleagues have shown that whole blood transfusion was associated with improved sur vival in children with severe falciparum malaria, and patients with impaired consciousness and hyperlactatemia benefted from transfusion even at moderate levels of anemia.