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Evidence supports the premise that maternal psychological distress adversely affects pregnancy outcomes and that inflammatory markers and placentally-produced corticotrophin-releasing hormone (pCRH) are likely mediating factors. The primary aim of the study was to explore the associations between maternal psychological distress, use of selective serotonin re-uptake inhibitors, pCRH, and maternal plasma inflammatory markers during pregnancy. Measures of maternal plasma pCRH, Interleukins-1, 6, & 10, C-Reactive Protein, Macrophage Migration Inhibitory Factor, and Tumor Necrosis Factor-αwere completed in 100 pregnant women. Measures of depression, anxiety, and perceived stress were completed, as well as collection of demographic/behavioral data, e.g. use of selective serotonin re-uptake inhibitors (SSRIs). Significant correlations were found at 14-20 weeks gestation between IL-6 & 10, and depression, anxiety, and perceived stress. Also at 14 - 20 weeks gestation, IL10 levels were significantly lower in women with 4th quartile pCRH levels and IL1β, IL6, and IL10 were significantly lower among women who took an SSRI during pregnancy. After controlling for maternal age, BMI, pCRH level, and SSRI use, psychological distress remained to explain variation in maternal inflammatory markers. These results might suggest that future research should focus on whether depression and anxiety are effectively being treated during pregnancy, and how such a scenario might contribute to an immune system pathway to poor pregnancy outcome.