Almost no research exists on the relationship between religion/spirituality (R/S) and health in the U.S. South Asian population. Using data from the joint Study on Stress, Spirituality, and Health and Mediators of Atherosclerosis Among South Asians Living in America Study (MASALA), this paper examined associations between self-rated R/S and self-rated health, emotional functioning, trait anxiety, and trait anger in a community-based sample (n = 933) from the Chicago and San Francisco Bay areas. OLS regression was used to analyze categorical differences in levels of R/S and ordinal trends for R/S, adjusting for potential confounders. Being slightly or moderately R/S was associated with lower levels of self-rated health compared to being very R/S, and being slightly or moderately R/S was associated with higher levels of anxiety. In both cases, there was no significant difference between very R/S individuals and non-R/S individuals, suggesting a curvilinear relationship. Self-rated R/S was not significantly associated with emotional functioning or anger. In sum, high-R/S and low-R/S individuals had positive associations with self-rated health and anxiety compared to individuals with slight/moderate levels of R/S. It is important for clinicians and policy makers to recognize the role R/S can play in the health status of South Asians living in the United States.