Although there is a fair sized literature documenting the relationship of religiousness and spirituality with health and well-being, far fewer studies have examined this phenomenon for people with serious mental illness. In this research, religiousness is defined as participation in an institutionalized doctrine while spirituality is framed as an individual pursuit of meaning outside the world of immediate experience. In this study, 1,824 people with serious mental illness completed self-report measures of religiousness and spirituality. They also completed measures of three health outcome domains: self-perceived well-being, psychiatric symptoms, and life goal achievement. Results showed that both religiousness and spirituality were significantly associated with proxies of well being and symptoms, but not of goal achievement. Implications of these findings for enhancing the lives of people with psychiatric disability are discussed.