Background The Center for Epidemiologic Studies Depression scale (CESD) was widely used for screening of depressive symptoms. The purpose of the current study was to investigate the factor structure and measurement invariance of the CESD across genders and groups in a sample of Chinese undergraduates and clinical patients. Methods Participants included 3093 undergraduates from the Hunan province and 336 patients from psychological clinics. The structure of the CESD scale was analyzed by

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... tory factor analysis (CFA). Multiple sets of CFAs were used to test measurement invariance across genders among undergraduates and clinical patients. Internal consistency reliability was also evaluated. Results The five-factor model achieved satisfactory fit (in the undergraduate sample: WLSMVχ2 = 1662.385, df = 160, CFI = 0.973, TLI = 0.968, RMSEA = 0.055; in the clinical patients: WLSMVχ2 = 502.089, df = 160, CFI = 0.962, TLI = 0.955, RMSEA = 0.072). The measurement invariance of the five-factor model across genders was supported fully assuming different degrees of invariance. The CESD also showed acceptable internal consistency. Conclusion Due to its sound structure and measurement invariance, the five-factor model of the CESD is best suited for testing in Chinese mainland college students and clinical patients.