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People with serious and persistent mental illnesses and/or substance use disorders are among the most economically and socially disenfranchised populations in Canada, and often present with long histories of labour market detachment and underemployment. Work engagement has the potential to improve social determinants of health while also harnessing productive capacity. This article reports on a five-year study examining the social, economic, and health impacts of Work Integration Social Enterprises (WISEs) in the mental health sector in Ontario, Canada. The findings shed light on the population that works in WISEs, its levels of social and labour market integration, and organizational features that influence worker outcomes. Results highlight both the importance of WISEs as a means of supporting employment, and challenges to organizational sustainability.