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Objective This study aimed to identify the effect of coronavirus disease (COVID-19)–related lifestyle changes on depression.Methods This secondary data analysis study included 229,269 adults from a community health survey conducted in the South Korea in 2020. Data were collected using a structured questionnaire about participants’ lifestyle changes related to COVID-19 and the Patient Health Questionnaire-9. The data were analyzed using a complex sample independent t-test, analysis of variance, Pearson’s correlation coefficient, and multiple regression analysis.Results The mean age of the participants was 48.76; 49.6% were male, and 50.4% were female. The multiple regression showed that depression increased due to COVID-19–related lifestyle changes (physical activity, sleep duration, consumption of convenience foods, alcohol consumption, smoking, and use of public transportation). The explanatory power was 27.3%, and the model was suitable (Wald F=63.75, p<0.001).Conclusion This study identified the effect of COVID-19–related lifestyle changes on depression, and the results have implications for future depression-relieving interventions.