Previous research indicates that racial discrimination is associated with negative mental health outcomes among Asian Americans, with mixed findings related to generational status and the relation of racism to multiple mental health outcomes simultaneously. To test whether generational status moderates relation between racism-related stress (RRS) and depression as mediated by anxiety and interpersonal sensitivity (IS). Two hundred twenty-two Asian American adults from a public university completed a survey. Measures included the Asian American Racism-Related Stress Inventory, the Depression, Anxiety, and IS subscales of the Brief Symptom Inventory, and demographic questions. Although RRS was related to mental health for the whole sample, disaggregation showed positive relations for RRS and mental health variables only for first-generation participants and not for 1.5 or second-generation participants. Generational status moderated the relation between RRS and depression as mediated by anxiety and IS only for first-generation participants. Post hocs that collapsed one-and-a-half- and second-generation participants into 1 group showed positive relations for RRS and IS, and mediation analyses indicated that IS is a possible mediator. The relation between RRS and mental health outcomes in Asian Americans differs based on generational status. Generational status should be considered in future research looking at the effects of RRS on mental health.