We examined participation in an ethnically based residential program or "theme house" during the first year of college as a predictor of downstream immune system inflammation among undergraduates. Using a 4-year prospective design, we compared markers of inflammation among Latino/Latina students in a residential theme program with a matched sample of nonresidents. Students provided oral mucosal transudate samples for the assessment of circulating Interleukin 6 (IL-6), an inflammatory cytokine linked to health vulnerabilities. Findings suggest a protective benefit of theme house residency especially among students with anxious expectations of discrimination. Such expectations predicted higher levels of IL-6 after the first year of college among nonresidents only. In years 2–3, following exit from the theme house, the relationship between expected discrimination and IL-6 levels remained positive among nonresidents and was attenuated among residents, controlling for past IL-6 levels. Culturally based spaces may therefore offset the physiological burden of expected discrimination among undergraduates.