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BackgroundAmong Latinos, living in a locality with greater Latino ethnic density may be protective for mental health, although findings vary by Latino subgroup, gender and birthplace. Although little studied, Latino residential segregation may capture different pathways linking risk and protective environmental factors to mental health than local ethnic density.MethodsThis study evaluated the association between residential segregation and mental distress as measured by the Kessler-10 (K10) among Latino participants in the National Latino and Asian American Study (NLAAS). Census data from 2000 was used to calculate metropolitan statistical area (MSA) residential segregation using the dissimilarity and isolation indices, as well as census tract ethnicity density and poverty. Latino subgroup (Puerto Rican, Mexican American, Cuban American and other Latino subgroup), gender and generation status were evaluated as moderators.ResultsAmong 2554 Latino participants in NLAAS, residential segregation as measured by the isolation index was associated with less mental distress (β −0.14, 95% CI −0.26 to −0.03 log(K10)) among Latinos overall after adjustment for ethnic density, poverty and individual covariates. Residential segregation as measured by the dissimilarity index was significantly associated with less mental distress among men (β −0.56, 95% CI −1.04 to −0.08) but not among women (β −0.20, 95% CI −0.45 to 0.04, p-interaction=0.019). No modification was observed by Latino subgroup or generation.ConclusionsAmong Latinos, increasing residential segregation was associated with less mental distress, and this association was moderated by gender. Findings suggest that MSA-level segregation measures may capture protective effects associated with living in Latino communities for mental health.