Low-income African-American women report elevated prenatal depressive symptoms more often (42 %) than the national average (20 %). In the USA in 2012, 16.5 % of African-American women experienced a premature birth (less than 36 completed gestational weeks) compared to 10.3 % of white women. In addition, 13 % of African-American women had a low-birth weight infant (less than 2,500 g) compared to 7 % of white women. Variation in the neuropeptide, oxytocin has been implicated in perinatal depression, maternal behavior, regulation of stress responses, and may be associated with this health disparity. The purpose of this investigation was to examine factors associated with prenatal depressive symptoms, including plasma oxytocin levels and birth weight, in a sample of urban African-American women. Pregnant African-American women (N = 57) completed surveys and had blood drawn twice during pregnancy at 15-22 weeks and 25-37 weeks. In addition, birth data were collected from medical records. A large number of participants reported elevated prenatal depressive symptoms at the first (n = 20, 35 %) and the second (n = 19, 33 %) data points. Depressive symptoms were higher in multigravidas (t(51) = -2.374, p = 0.02), women with higher anxiety (r(47) = 0.71, p = 0.001), women who delivered their infants at an earlier gestational age (r(51) = -0.285, p = 0.04), and those without the support of the infant's father (F(4, 48) = 2.676, p = 0.04). Depressive symptoms were also higher in women with low oxytocin levels than in women with high oxytocin levels (F(2, 47) = 3.3, p = 0.05). In addition, women who had low oxytocin tended to have infants with lower birth weights (F(2, 47) = 2.9, p = 0.06). Neither prenatal depressive symptoms nor prenatal oxytocin levels were associated with premature birth. Pregnant multigravida African-American women with increased levels of anxiety and lacking the baby's father's support during the pregnancy are at higher risk for prenatal depressive symptoms. Prenatal depressive symptoms are associated with low oxytocin levels and lower infant birth weights. Further research is needed to understand the mechanisms between prenatal depressive symptoms, oxytocin, and birth weight in order to better understand this health disparity.