While there is good evidence that depression negatively impacts mother-to-infant emotional attachment in the postpartum period, the impact of depression in pregnancy on maternal emotions and cognitions about the fetus (often termed "maternal-fetal attachment" or MFA) is unclear. This study compared MFA scores from women meeting clinical criteria for Major Depressive Disorder (MDD) with scores from nondepressed women. Participants were 161 women enrolled at 23-36 weeks gestation, of whom 65 met criteria for MDD via the Structured Clinical Interview for the DSM-IV-TR during their second and/or third trimesters. Cranley's Maternal Fetal Attachment Scale was administered at 26 and 36 weeks gestation. Generalized linear modeling was used to assess the effect of MDD, anxiety, and antidepressant use on MFA. MDD was negatively related to MFA (LR) = 4.58, df = 1, p < 0.04). Neither anxiety (LR = 0.22, p < 0.64), nor antidepressant use (LR = 0.20, df = 1, p < 0.66) were related to MFA. Depression severity was negatively related to MFAS scores (B = -0.005, SE = .002, p < 0.0012) when including the interaction of MDD group and HRSD scores in the model. This study is the first to demonstrate that clinically defined MDD during pregnancy negatively impacts MFA, suggesting that the basis for poor mother-to-infant attachment in postpartum MDD may have roots in pregnancy.