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Few studies have documented the pathways through which individual level variables mediate the effects of neighborhoods on health. This study used structural equation modeling to examine if neighborhood characteristics are associated with depressive symptoms, and if so, what factors mediated these relationships. Cross-sectional data came from a sample of mostly rural, older adults in North Carolina (n = 1,558). Mediation analysis indicated that associations among neighborhood characteristics and depressive symptoms were mediated by loneliness (standardized indirect effect = −0.19, p < 0.001), physical activity (standardized indirect effect = −0.01, p = 0.003), and perceived individual control (standardized indirect effect = −0.07, p = 0.02) with loneliness emerging as the strongest mediator. Monitoring such individual mediators in formative and process evaluations may increase the precision of neighborhood …