Pediatricians are paying increased attention to the effects of socioeconomic status (SES) on children's health. Low SES is a robust predictor of obesity across the life course and may interact with genes affecting metabolism to influence obesity risk. Recent animal literature and burgeoning human research suggest that the hormone oxytocin (OT) may be important for metabolic regulation. To date, this association has not been examined in children. To examine whether an OT receptor polymorphism (rs53576) interacts with SES, potentially exacerbating and buffering the effects of stress, to predict anthropometry during childhood, and based on differential neurobiological susceptibility theory, to test whether carriers of the A allele of the OXTR gene, compared with GG genotyped individuals, would be most sensitive to the effects of SES on anthropometry for better or for worse. In this observational study, families were recruited from public school classrooms and enrolled in the Peers and Wellness Study (PAWS), which examined the effects of social status on health. Families were assessed during children's kindergarten year (fall semester of 2003, 2004, and 2005) and again during middle childhood (2009-2011) for a follow-up assessment that included anthropometric measures and DNA collection. The dates of the analysis were January 2015 to June 2016. Socioeconomic disparities. Child body mass index z score (BMIz) and triceps skinfold thickness. Family SES was collected through questionnaires mailed to homes. Body measurements and DNA were collected in homes by trained research assistants. From the original community sample of 338 typically developing children, participants were 186 socioeconomically and racially/ethnically diverse children (mean age, 10.3 years; age range, 9.4-11.3 years; 93 females [50%]) who had sufficient data at the follow-up assessment for inclusion in this study. Among 97 A allele carriers, a 1-SD increase in SES was associated with a decrease in BMIz of 0.28 (95% CI, -0.47 to -0.09) and a decrease in skinfold thickness of 0.95 (95% CI, -1.77 to -0.12) mm, such that they exhibited the highest BMIz and skinfold thickness in contexts of low SES but exhibited the lowest BMIz and skinfold thickness in contexts of high SES. Socioeconomic status was unrelated to BMIz (95% CI, -0.21 to 0.26) or skinfold thickness (95% CI, -0.42 to 1.45) for 89 GG genotyped children. These findings advance etiologic understanding of childhood obesity, highlighting complex effects of SES on child health and adding to growing evidence that OT relates to human obesity risk. The results also support differential neurobiological susceptibility theory, suggesting that the A allele renders individuals more sensitive to both positive and negative health effects of socioecological context.