Objective To analyze the mediating effects of the sense of coherence between mental stress and depression in stroke patients, and to offer guidance and assistance to reducing mental stress and depression and improving mental health in stroke patients. Methods Totally 468 stroke patients were selected from the Department of Neurology of a ClassⅢ Grade A hospital in Zhengzhou by convenient sampling between July 2016 and July 2017 and investigated with Sense of Coherence Scale (SOC-13) , Chinese Perceived Stress Scale (CPSS) and Center for Epidemiologic Studies Depression Scale (CES-D) . The data were statistically analyzed with SPSS 21.0 and AMOS 22.0. Results The total average scores for SOC-13, CPSS and CES-D in these stroke patients were (63.39±9.92) , (41.65±7.29) and (23.80±4.20) , respectively. The sense of coherence was negatively correlated with mental stress and depression (r=-0.47, -0.51; P<0.01) , and mental stress was positively correlated with depression (r=0.52, P<0.01) . As a meditating variable, the sense of coherence reduced the adverse prediction effects of mental stress on depression from 0.632 to 0.283. According to the re-analysis of the structural equation model, the sense of coherence was the mediating variable between mental stress and depression. The fit indexes were good (χ2/df=2.450, GFI=0.942, AGFI=0.941, CFI=0.940, TLI=0.922, RMSEA=0.052, RMR=0.036) . Conclusions As the mediating effect between mental stress and depression, the sense of coherence reduces the adverse prediction effects of mental stress on depression to some extent. Therefore, the sense of coherence in stroke patients shall be enhanced to improve their mental health and reduce the incidence of depression. Key words: Stroke; Depression; Sense of coherence; Mental stress; Mediating effect