This cross-sectional study examines the association between psychosocial risk factors and stress-related disorders (SRDs) among 267 chemical laboratory workers across academic, industry, and government sectors in Sri Lanka. Utilizing the Laboratory Safety Culture Survey, Copenhagen Psychosocial Questionnaire II (COPSOQ-II), and General Health Questionnaire (GHQ-12), findings reveal that 36.3% of participants were likely to experience SRDs. Health and safety concerns emerged as the most significant predictor, increasing SRD likelihood by 55.7%, while emotional demands were also influential. Notably, a faster work pace reduced stress levels by 11.6%. Protective factors included recognition and supervisor support, which lowered SRDs by 15.4% and 16.7%, respectively. Sociodemographic factors such as education, job role, and chemical handling experience also significantly affected mental health. Industry workers exhibited higher SRD prevalence than their academic and government counterparts. These results emphasize the need for targeted safety measures, mental health support, and interdisciplinary research to improve laboratory worker’s well-being.