The independent and joint association of physical activity (PA) and weekday sleep duration with metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear. Aims: We intended to explore this association in the United States.

This cross-sectional study recruited 4974 individuals from the National Health and Nutrition Examination Survey between 2017 and 2018. Information regarding PA and weekday sleep duration was obtained through questionnaires. Metabolic associated fatty liver disease (MAFLD) was diagnosed by transient elastography based on the consensus definitions. Multivariable logistic regression models were employed to investigate the independent and joint association of PA and weekday sleep duration with MAFLD.

Of the 4974 subjects, engaging in active PA or sustaining adequate sleep duration was associated with decreased the odds of MAFLD (p < 0.05). Specifically, active leisure-time PA was linked to lower 37 % odds of MAFLD (OR, 0.63; 95 % CI, 0.55–0.73). Individuals who had one to twice times (150–299 min/week) or more than twice (≥300 min/week) the recommended amount of leisure-time PA by PA Guidelines had 19 % (OR, 0.81; 95 % CI, 0.67–0.99) and 45 % (OR, 0.55; 95 % CI, 0.47–0.65) lower odds of MAFLD, respectively (P for trend <0.001). Individuals with adequate weekday sleep duration was associated with 24 % lower odds of MAFLD (OR, 0.76;95 % CI,0.67–0.88). Notably, active PA combined with adequate weekday sleep duration significantly decreased the odds ratios for MAFLD by 35 % (OR: 0.65, 95 % CI, 0.52–0.80). However, in individuals with significant alcohol use, the joint effect of total PA and weekday sleep duration on MAFLD was not statistically significant.

Both active PA and adequate weekday sleep duration were inversely associated with the risk of MASLD independently, while combining them could further lower the risk of MASLD.