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Background Epidemiological data evaluating sleep problems in clinical nurses in mainland China are scarce and an association between sleep problems and occupational stress has not been investigated. Aims To assess the prevalence of sleep problems and associated factors and determine their association with occupational stress among clinical nurses in general hospitals. Methods Nurses were selected through random cluster sampling. They answered a self-administered questionnaire, which included sociodemographic and occupational variables, the Pittsburgh Sleep Quality Index (PSQI) scoring system and the Job Content Questionnaire for evaluating occupational stress. Logistic regression analysis was used to evaluate factors associated with sleep problems. Results There were 5012 participants. Mean PSQI score of 4951 subjects included in the final analysis was 7.32 ± 3.24, with 2713 subjects having PSQI ≥8, accounting for 55% of participants. Female subjects in the intensive care unit and emergency departments were at higher risk of sleep problems. The following factors also presented a risk for sleep problems: multiple years of service, high monthly night shift frequency, primary and intermediate professional status, temporary employment status and high occupational stressors (including high psychological job demands, low job control and low workplace's social support). Conclusions The overall prevalence rate of sleep problems among clinical nurses in general hospitals in mainland China was high. Many factors could affect the sleep quality of nurses, although occupational stress facilitates development of sleep problems. Various risk factors associated with sleep problems among nurses should be studied extensively and measures for relieving occupational stress should be undertaken. [ABSTRACT FROM AUTHOR]