Statins are a family of lipid-lowering drugs widely used to control cholesterol levels and prevent stroke and cardiac failure. Recently, they have demonstrated pleiotropic cholesterol-independent effects, such as neuroprotection after stroke and improved survival after septic insult. We hypothesized that statins could be potential drugs for acute cerebral infectious diseases like cerebral malaria caused by Plasmodium falciparum. In a clinically relevant murine model, we tested several statins (pravastatin, fluvastatin, simvastatin, and atorvastatin) alone or in combination with artesunate. Surprisingly, all statins used alone failed to prevent death from cerebral malaria and had no effect on parasitemia. However, the combination of atorvastatin and artesunate significantly improved survival on day 13 postinfection compared to atorvastatin alone (P=0.02, log rank test). Our observations suggest that statins should not be considered a panacea for cerebral malaria but rather have an adjuvant effect. Given that pleiotropic effects may depend on disease pathophysiology and patient status, convincing clinical trials are needed to explore the scope of these drugs, and their safety when administered after insult also requires attention.