This study examined the potential mediating role of racism-related stress and the potential moderating role of generational status in the experience of discrimination for 210 South Asians in the United States. Participants completed a demographic questionnaire, the General Ethnic Discrimination Scale (H. Landrine, E. A. Klonoff, I. Corral, S. Fernandez, and S. Roesch, 2006, Conceptualizing and measuring ethnic discrimination in health research, Journal of Behavioral Medicine, Vol. 29, pp. 79-94), the Rosenberg Self-Esteem Scale (M. Rosenberg, 1965, Society and Adolescent Self-Image, Princeton, NJ: Princeton University Press), and the Satisfaction with Life Scale (SWLS; E. Diener, R. A. Emmons, R. J. Larsen, & S. Griffin, 1985, The satisfaction with life scale, Journal of Personality Assessment, Vol. 49, pp. 71-75). The hypothesized structural equation model fit well for first-and second-generation South Asians, yet mediation and moderation were not supported. Perceived discrimination significantly related to perceived stress for both groups of South Asians. Implications for theory, research, and practice are discussed.