Objective To explore the effects of sleep deprivation on fatty degeneration, cholesterol and triglyceride contents and hepatic function in mice. Methods Mice were randomly divided into WT group and chronic sleep restriction group (CSR group). In the CSR group, mice were deprived of sleep for 20 hours a day for 7 days. Mice in the control group were free to sleep for 7 days under the same conditions. Seven days later, HE staining, oil red staining and BIODIPY staining were used to observe the fatty degeneration of mice's liver, and the changes of total cholesterol (TC) and triglyceride (TG) in liver tissue were observed by using ELISA kits. The changes of liver function were evaluated by detecting the activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum of two groups of mice. Results Compared with WT group, the mice in CSR group showed fatty degeneration of liver, and the contents of TC and TG in liver tissue increased significantly (P<0.01), and the concentrations of ALT and AST in serum increased (P<0.01). Conclusion Chronic sleep restriction can cause the deposition of TC and TG in liver tissue of mice, which lead to hepatic steatosis and liver function damage