OBJECTIVES: Sleep problems (SP) are prevalent among small-scale miners, yet little is known about their psychological and occupational determinants. We examined the association between work-related stress (WRS) and SP among small-scale miners in Ghana and explored the mediating roles of anxiety and depression in this association. METHODS: In this community-based cross-sectional study, data were collected from 664 miners in Obuasi,Ghana. WRS and SP were assessed using the Perceived Stress Scale (PSS-4) and the WHO Disability Assessment Schedule 2.0 (WHODAS 2.0), respectively, while anxiety and depression were measured using the GAD-7 and PHQ-9. Adjusted multivariate regressions and bootstrapped serial mediation models (Hayes' PROCESS Model 6) evaluated the hypothesized pathways. RESULTS: The mean (SD) age was 28.8 (8.2) years, and 84.3% were males. WRS was significantly associated with SP (B = 0.2964, 95% CI = 0.2398-0.3530), with both direct (42.5%) and indirect (57.5%) effects. Anxiety mediated 38.0% of the total effect, depression 11.4%, and the anxiety-depression pathway 8.1%. CONCLUSIONS: The study findings suggest that anxiety and depression serially mediate the WRS-SP link. These results underscore the need to address occupational stressors and incorporate mental health support into workplace policies to improve sleep quality and overall well-being in this vulnerable workforce.