ObjectiveTo investigate the causal association of liver function and lipid metabolism levels with sleep disorders based on the Mendelian randomization analysis. MethodsThe analysis was conducted using the data from genome-wide association studies， with the exposure factors of liver function and lipid metabolism levels （alanine aminotransferase ［ALT］， aspartate aminotransferase ［AST］， gamma-glutamyl transpeptidase ［GGT］， albumin ［Alb］， serum total protein ［TP］， total bilirubin ［TBil］， alkaline phosphatase ［ALP］， triglyceride ［TG］， triglyceride-to-glycerol-3-phosphate ［TG/G3P］ ratio， total cholesterol ［TC］， high-density lipoprotein cholesterol ［HDL-C］， low-density lipoprotein cholesterol ［LDL-C］， poly-unsaturated fatty acids ［PUFA］， total fatty acids ［TFA］， PUFA/TFA ratio） and the outcome factor of sleep disorders （nonorganic）. The regression models including inverse variance weighted， MR-Egger， Simple mode， weighted median， and Weighted mode were used to perform the Mendelian randomization analysis. ResultsSerum Alb （odds ratio ［OR］=0.728， 95% confidence interval ［CI］： 0.535 ‍—‍‍ 0.989， P<0.05）， HDL-C （OR=0.879， 95%CI： 0.784 ‍—‍ 0.986， P<0.05）， and PUFA/TFA ratio （OR=0.800， 95%CI： 0.642 — 0.998， P<0.05） were negatively associated with sleep disorders， while TG/G3P ratio （OR=1.222， 95%CI： 1.044 ‍—‍ 1.431， P<0.05） was positively associated with sleep disorders. The results of Mendelian randomization did not show a causal association of ALT， AST， GGT， TP， TBil， ALP， TG， TC， LDL-C， PUFA， and TFA with sleep disorders （all P>0.05）. The results of the MR-Egger intercept test showed no pleiotropy （P>0.05）， and Mendelian randomization was a valid method for causal inference in this study. ConclusionAccording to the results of the Mendelian randomization analysis， liver function and lipid metabolism show significant association with sleep disorders. Liver function and lipid metabolism can be used as indicators for predicting the risk of sleep disorders and performing intervention.