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Cerebral malaria (CM) is a serious and fatal malaria-associated syndrome caused by the development of an overwhelming proinflammatory response. Vitamin D (Vit.D; cholecalciferol) has regulatory functions associated with both innate and adaptive immune responses. Prevention is better than cure, in this experiment, we evaluated prophylactic oral Vit.D as a means of preventing CM presentation before infection of C57BL/6 mice with Plasmodium berghei ANKA (PbA) by modulating the host proinflammatory response. Mice that were supplemented with oral Vit.D has reduce death rate and ameliorated the integrity of the blood brain barrier. Prophylactic oral vitamin D relieved the symptoms of brain malaria and avoided death, gained valuable time for the diagnosis and treatment post infection. The robust Th1 response was attenuated in the Vit.D + PbA group. Furthermore, T-cell trafficking to the brain was diminished before PbA infection using Vit.D. The results suggest that Vit.D supplementation mediates the development of an anti-inflammatory environment that improves CM severity. In summary, the use of Vit.D as a nutritional supplement in malaria-endemic regions may help reduce the severity and mortality of CM.Preventive treatment of vitamin D alleviated the symptoms of cerebral malaria.Preventive treatment of vitamin D reduces production of proinflammatory cytokines in spleens and sera.Preventive treatment of vitamin D inhibited Th1 immune response.