While the segmentation of residential areas by race is well known to affect the social and economic well-being of the segregated minority group in the United States, the relationship between segregation and health has received less attention. This study examines the association between racial residential segregation, as measured by the isolation index, and individual weight status in US metropolitan areas. Multi-level, nationally representative data are used to consider the central hypothesis that segregation is positively associated with weight status among African Americans, a group that is hyper-segregated and disproportionately affected by unhealthy weight outcomes. Results show that among non-Hispanic blacks, higher racial isolation is positively associated with both a higher body mass index (BMI) and greater odds of being overweight, adjusting for multiple covariates, including measures of individual socioeconomic status. An increase of one standard deviation in the isolation index is associated with a 0.423 unit increase in BMI (p < 0.01), and a 14% increase in the odds of being overweight (p < 0.01). Among whites, there is no significant association between the isolation index and weight status. These findings suggest that in addition to differences among people, differences among places and, in particular, differences in the spatial organization of persons may be relevant to health policy and promotion efforts.