Background: Chronic rapid eye movement (REM) sleep deprivation negatively impacts memory, which was related to oxidative stress induced damage and decreased level of brain derived neurotropic factor (BDNF). Vitamin D is a neurosteroid known for its antioxidant properties.Aim of the study: The current work is designed to assess the antioxidant role of vit D on the experimental model of REM sleep deprivation induced memory impairment. Also, to investigate the modulatory effect of vitD on the possible expected disturbance in the level of BDNF associated with such condition. Material and Methods: Chronic sleep deprivation was induced via placing rats in a modified multiple platform apparatus for 8 h/day for 6 weeks. Concomitantly, vit D was administered to animals at doses of 500 IU/kg/day by oral gavage. After 6 weeks of treatment, the Morris water maze (MWM) was used to test for spatial learning and memory performance. The hippocampus was dissected; and levels/activities of antioxidant defense biomarkers, superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GPx) and BDNF level were evaluated Results:Chronic REM sleep deprivation impaired spatial memory (P<0.05) which was prevented by vit D treatment, also vit D normalized sleep deprivation induced decrease in hippocampal SOD (P<0.05) and BDNF (p<0.001) and increase in MDA (p<0.001). Conclusion: Spatial memory impairment was induced by chronic REM sleep deprivation and vit D treatment prevented such impairment. This was possibly achieved via normalizing antioxidant defense mechanisms and BDNF level in hippocampus.