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Objective: To investigate the prevalence of sleep disturbance in outpatients with chronic pain and evaluate the mediating effect of depressive symptoms on the association between sleep disturbance and pain severity. Methods: A cross-sectional survey was conducted in 2023 in outpatients with chronic pain from medical institutions in Beijing, Jiangxi, and Chongqing based on multistage stratified sampling. The patients who were aged ≥45 years and had pain duration ≥3 months were included. The information about their sociodemographic characteristics, pain severity, sleep status, and depressive symptoms were collected by using structured questionnaires. Correlation analysis and multiple linear regression models were applied to evaluate the association between sleep disturbance and pain severity. After controlling for potential confounders, a mediation effect model was used to analyze the mediating effect of depressive symptoms. Results: A total of 4 151 study participants were included. Sleep disturbance was identified in 1 784 participants (42.98%), and depressive symptoms were identified in 378 participants (9.11%). Moderate pain was reported by 2 535 participants (61.07%), mild pain by 1 079 participants (25.99%), and severe pain by 537 participants (12.94%). Sleep disturbance was positively associated with pain severity (r=0.239, P<0.001), and sleep disturbance was also positively associated with depressive symptoms (r=0.186, P<0.001); depressive symptoms were likewise positively associated with pain severity (r=0.235, P<0.001). After adjustment for covariates, each one-point increase in the sleep disturbance score was associated with a 0.287-point increase in the Patient Health Questionnaire-2 (PHQ-2) score (β=0.287), and each one-point increase in the sleep disturbance score was associated with a 0.156-point increase in the pain score (β=0.156). After depressive symptoms were added to the model, the direct effect of sleep disturbance on pain severity remained significant (β=0.143), and each one-point increase in the PHQ-2 score was associated with a 0.048-point increase in the pain score (β=0.048). Depressive symptoms partially mediated the association between sleep disturbance and pain severity, accounting for 8.75% of the total effect. Conclusions: The prevalence of sleep disturbance was high in outpatients with chronic pain in Beijing, Jiangxi, and Chongqing. Sleep disturbance was associated with pain severity and might be also indirectly associated with pain severity through depressive symptoms. In clinical practice, more attention should be paid to the comprehensive assessment and management of sleep quality and emotional status in patients with chronic pain to mitigate pain severity and improve overall health outcomes.