Background: Latinas in the United States suffer disproportionately high levels of pre- and postnatal depression. However, little is understood regarding the biopsychosocial mechanisms linking socio-environmental factors to this increase in mental health risk. The oxytocinergic system, with its roles in the stress response, social behaviour and mood regulation, may be an important modulator of this sensitivity. We have previously reported prenatal discrimination to be a significant predictor of postnatal depression in Latinas; here we tested whether sensitivity to discrimination stress might depend on oxytocinergic system activity. Methods: A sample of 148 Latina women residing in the US were assessed prenatally at 24-32 weeks' gestation and 46 weeks postnatally for perceived discrimination levels, acculturation, and depression and anxiety symptoms. Plasma oxytocin (OXT) levels and DNA methylation of the oxytocin receptor (OXTR) were measured prenatally together with genotyping for the OXTR SNP, rs53576. Results: In mothers with low OXT levels and low OXTR methylation, acculturation level was associated with postnatal depression and anxiety symptoms. No such associations were found in those with higher OXT levels and higher OXTR methylation. We also found a significant relationship between prenatal psychosocial factors (discrimination and acculturation) and postnatal depression and anxiety in carriers of the G-allele at rs53576, but not AA genotypes. Finally, OXTR methylation positively correlated with mothers reports of experiencing affiliative social touch. Moreover, social touch mediated the relationship between discrimination and postnatal depression in those with low OXTR methylation. Conclusion: These results support the hypothesis that the oxytocinergic system modulates sensitivity to prenatal stress in the development of postnatal mood and anxiety disorders in Latina mothers