Although there is good evidence that sedentary behavior is associated with poor health outcomes in healthy persons and patients with cardiovascular disease, the mental health consequences of sedentary behavior have not been widely studied. In this report, we conducted a cross-sectional analysis to examine the relation of self-reported sedentary behavior and depression in a sample of 4,043 hospitalized men and women with acute coronary syndrome enrolled in a randomized clinical trial in rural China. Sedentary behavior was assessed by self-report, and depression was assessed with the Patient Health Questionnaire-9 (PHQ-9); a subset of 1,209 patients also completed the Beck Depression Inventory-II. Results revealed that greater sedentary behavior was associated with higher levels of depressive symptoms measured by both the PHQ-9 (p <0.001) and the Beck Depression Inventory-II (p <0.001). Compared with patients who reported that they were seldom sedentary, patients reporting that they were frequently sedentary were 4.7 times (odds ratio 4.73, 95% confidence interval 2.71 to 8.24) more likely to be clinically depressed defined as PHQ-9 scores ≥10 after adjusting for demographic factors, lifestyle behaviors, clinical characteristics, and in-hospital treatments. In conclusion, greater sedentary behavior is significantly related to greater depression in Chinese patients with acute coronary syndrome, independent of physical activity. These findings suggest that strategies to reduce sedentary behavior may improve medical outcomes and reduce risk for depression.