Objective To investigate the effects of vitamin D (VD) on the cognitive function of sleep‑deprived (SD) mice and related mechanisms. Methods According to the random number table, 40 C57BL/6 mice were divided into four groups (n=10): a normal control (Ctrl) group, an SD group, an SD+VD (VD) group, and an SD+VD+3MA (3MA) group. Mice in the Ctrl group did not receive any intervention, while those in the SD group, VD group and 3MA group were deprived of sleep for 72 h through the multi‑platform water environment method. The VD group and 3MA group were intraperitoneally injected with 1.5 μg/kg of 1, 25‑dihydroxy vitamin D3 [1,25(OH)2D3] for consecutive seven days; the 3MA group was injected with an autophagy inhibitor 3MA at 2 mg/kg for consecutive seven days; and the Ctrl group and SD group were intraperitoneally injected with the same amount of normal saline. After modeling, Morris water maze was used to examine the learning and memory ability of the mice. After the behavioral test, the mice were sacrificed and samples were collected. The enzyme‑linked immunosorbent assay (ELISA) kit was used to detect the content of 25‑hydroxy vitamin D3 (25HVD3) in serum and the expression of amyloid β‑protein (Aβ), tumor necrosis factor‑α (TNF‑α), interleukin (IL)‑6 and IL‑1β in the hippocampus. Western blot was used to detect the expression of the autophagy‑related markers, Beclin 1, a mammalian homologue of yeast Atg6, and B subunit of microtubule‑associated protein light chain 3 (LC3B) in the hippocampus. LC3B was labeled by immunofluorescence staining. Results Compared with the Ctrl group, the VD group, SD group and 3MA group presented remarkable increases in the escape latency, decreases in the number of times crossing the target platform and the time spent in target quadrant, decreases in the content of serum 25HVD3, increases in the levels of hippocampal Aβ, TNF‑α, IL‑1β, IL‑6 and hippocampal Beclin 1 and LC3B (P<0.05), with enhanced expression of green fluorescence. Compared with the SD group, the VD group showed decreases in the escape latency, and increases in the number of times crossing the target platform and the time spent in target quadrant (P<0.05); the VD group and 3MA group presented increases in the content of serum 25HVD3, and decreases in the levels of hippocampal Aβ, TNF‑α, IL‑1β, and IL‑6 (P<0.05); and the VD group presented obvious increases in the levels of hippocampal Beclin 1 and LC3B (P<0.05), with enhanced expression of green fluorescence. Compared with the VD group, the 3MA group presented remarkable increases in the escape latency, decreases in the number of times crossing the target platform and the time spent in target quadrant, increases in the levels of hippocampal Aβ, TNF‑α, IL‑1β and IL‑6, and decreases in the levels of Beclin 1 and LC3B (P<0.05), with weakened expression of green fluorescence. Conclusions Vitamin D improves the cognitive function of sleep‑deprived mice, which may be related to the activation of autophagy.