Background Mental disorders remain the most significant contributor to years lived with disability in South Asia, yet governmental health expenditure on mental health in South Asia remains very low with limited strategic policy development. To strengthen the case for action it is important to better understand the profound economic costs associated with poor mental health. Methods: We conducted a systematic review on the costs of all mental disorders, as well as intentional self-harm and suicide, in the World Bank South Asia Region. Ten global and South Asian databases as well as grey literature sources were searched. Results: 72 studies were identified, including 38 meeting high quality criteria for good reporting of costs. Of these, 27 covered India, five Pakistan, four Nepal and three Bangladesh and Sri Lanka. Most studies focused on depressive disorders (15), psychoses (14) and harmful alcohol use (7); knowledge of economic impacts for other conditions was limited. Profound economic impacts within and beyond health care systems were found. In 15 of 18 studies which included productivity losses to individuals and/or carers, these costs more than outweighed costs of health care. Conclusion: Mental disorders represent a considerable economic burden, but existing estimates are conservative as they do not consider long-term impacts or the full range of conditions. Modelling studies could be employed covering longer time periods and more conditions. Clear distinctions should be reported between out-of-pocket and health system costs, as well as between mental health service-specific and physical health-related costs.