Hospital work involves some of the most stressful situations found in any workplace. Furthermore, hospital workers may be affected by non-work-related stress such as family responsibilities and financial difficulties, leading to impaired mental well-being and suboptimal performance. The aim of this study was to assess the level of general mental well-being among doctors and nurses from two hospitals in Kingston, Jamaica. A total of 212 doctors and nurses at the Kingston Public Hospital and the University Hospital of the West Indies were studied yielding a participation rate of 83.1%. A self-administered questionnaire was used to gather social and biomedical data and the General Health Questionnaire 30 (GHQ 30) used to determine general mental well-being. Probable caseness was defined as a GHQ 30 score > 5. Focus group discussions were also held with staff at both hospitals. A total of 27.4% of the study population met the GHQ-30 criteria (caseness) defining them as probable cases of mental distress. Cases and non-cases were not different in age, gender or hospital of employment. However, caseness was associated with years of professional experience, work-related and non-work-related stress, serious financial difficulties and fears of coming to work. Significant predictors of increased risk of caseness were fear of coming to work (OR 3.06; CI 1.40, 6.70); professional experience in excess of five-years and high non-work-related stress. High work-related stress was associated with reduced risk of being classified a case, suggesting that work may have been therapeutic. Focus group discussions suggested that non-work stress was related to financial difficulties, commuting and child care, especially among nurses. Intervention to improve general mental well-being should be targeted at new employees and should address child care, commuting and financial management.