To study the effects and mechanisms of Nano-Se on cognition performance after sleep deprivation(SD) in mice.A total of 120 male mice were randomly divided into 2 batches.The first batch of 24 mice was randomly divided into 3 groups:control(NC),Na₂SeO₃(SE) and Nano-Se(NS).These mice were administered respectively with SE and NS(1 μg/d,2 μg/d,4 μg/d) by intra-gastric injection for 30 days,then their Se content and GSH-Px activity in blood were measured; The second batch of 96 mice were randomly divided into 4 large groups:control(N-SeC) and low,middle,high Nano-Se groups(L,M,H).Nano-Se solutions(2 μg/ml,4 μg/ml,8 μg/ml)were administered(0.5 ml/d) to mice of L,M and H groups respectively by intra-gastric injection for 30 days,and the control group was administered with distilled water.Each large group was divided into 4 groups:SD control(SDC),SD18h,SD36h and SD54h.SD model was induced in mice by single platform technique.In the SD mice,the cognitive ability of the mice were tested by Y-maze.Further,brain GSH-Px,NO and MDA levels were measured.Blood GSH-Px activity was enhanced by Nano-Se compared to SE group,but the blood Se content was not different.SD decreased cognitive ability and GSH-Px activity,but increased NO and MDA levels.Compared to N-SeC,Nano-Se improved cognitive ability,increased GSH-Px activities,while decreased NO levels in M and H groups.MDA reduction was found in H group only.Our data suggest that Nano-Se could improve cognitive ability of mice,the mechanism of which might involve the increased GSH-Px activity and decreased free radical content.