The current study examined associations of social and built features of neighborhood environments with psychological distress 6 years later and whether these associations were explained by stress and social factors, among Hispanic/Latino adults from the HCHS/SOL and SOL CASAS Ancillary Study. In the SOL CASAS Ancillary Study, HCHS/SOL San Diego participants' baseline (2008-2011) home addresses were geocoded, neighborhoods were defined using 800m radial buffers, and variables representing neighborhood socioeconomic deprivation, social disorder, walkability, and greenness were created. Psychological distress (anxiety and depression symptoms) and proposed pathway variables chronic stress, social support, and family cohesion were assessed at HCHS/SOL Visit 2 (2014-2017). On average, the population (n = 2785) was 39.47 years old, 53.3% were women, and 92.3% were of Mexican heritage. In complex survey regression analyses that accounted for sociodemographic covariates, the complex sampling design, and sample weights, greater baseline neighborhood socioeconomic deprivation predicted lower family cohesion at Visit 2 (B = -0.99, 95% CI [-1.97, -0.06]). Path models showed indirect associations of baseline neighborhood socioeconomic deprivation with Visit 2 psychological distress through family cohesion (MacKinnon's 95% CI depression [0.001, 0.026]; 3.9% of the variance accounted for; anxiety [0.00071, 0.019] 3.0% of the variance accounted for). Among adults of mostly Mexican heritage from the San Diego, CA area, neighborhood deprivation indirectly predicted later psychological distress through family cohesion. No other effects of neighborhood variables were observed.