Purpose: This study aimed to identify the relationship between cognitive function and activities of daily living (ADL) in addition to the mediating effect exerted by depression on this relationship in post-stroke patients.Methods: A cross-sectional study was performed. A total of 182 patients were recruited from two general and three geriatric hospitals in South Korea between July 2017 and June 2018. Cognitive function, depression, and ADL measures were assessed after informed consent was obtained. Data obtained were analyzed using multiple regression and a simple mediation model that applies the PROCESS macro with a 95% bias-corrected bootstrap confidence interval (5,000 bootstrap resampling).Results: The covariates were sex, age, educational level, types of paralysis, and type of hospital. After controlling for the demographic covariates, cognitive function significantly accounted for the variance of ADL. It was also demonstrated that depression partially mediated the relationship between cognitive function and ADL in post-stroke patients.Conclusion: Cognitive function directly influences the ADL in post-stroke patients and indirectly influences it through depression. This suggests that strategies for improving depression in post-stroke patients should be considered while managing cognitive functioning for improving the ADL.