Perinatal depression negatively impacts mother-infant health and well-being. Previous work has linked cortisol reactivity to perinatal depressive symptoms, but moderating effects including social support and neuroticism, have not been studied. Forty-nine pregnant women (9-30 weeks' gestational age; GA) provided saliva samples in response to the Trier Social Stress Test (TSST) and to awakening (cortisol awakening response, CAR), and completed questionnaires on perceived social support, personality, and depressive symptoms. Two hierarchical logistic regressions, one including the TSST response and one including the CAR as predictor variables, suggest that cortisol reactivity, social support from the baby's father, and neuroticism contribute to depressive symptoms, controlling for GA (both p < .01). Significant statistical interactions among predictors of pregnancy depressive symptoms were, however, only found in the model using the CAR. Findings highlight the importance of considering biopsychosocial interactions in studies predicting perinatal depressive symptoms.