Objective This study aims to examine the association between leptin and postpartum depression symptoms. Methods Two hundred pregnant women were enrolled and their prenatal serum leptin levels were measured by using enzyme-linked immunosorbent assay (ELISA). The state of depression was first assessed on the third day after delivery and reassessed by a telephone follow up on the 42nd day using the Edinburg postnatal depression scale (EPDS) after delivery. Patients with postpartum depression symptoms with EPDS score ≥13 points after 3 days postpartum or 42 days postpartum were recruited as the depressive symptom group. Results The medians and lower and upper quartiles of the prenatal serum leptin levels in the depressive symptom group (the 3rd day) and the control group were 1.36 (1.15, 1.68) μg/L and 1.49 (1.28, 1.91) μg/L, respectively. After normal conversion, the serum leptin level was significantly lower in the depressive symptom group than in the control group (P=0.021). The medians and lower and upper quartiles of the prenatal serum leptin levels in the depressive symptom group (the 42nd day) and the control group were 1.17 (1.01, 1.36) μg/L and 1.50 (1.29, 1.90) μg/L, respectively. After normal conversion, the serum leptin level was significantly lower in the depressive symptom group than in the control group (P＜0.001). EPDS scores 3 days postpartum (r=-0.199, P=0.014) and 42 days postpartum (r=-0.254, P=0.002) were negatively correlated with prenatal serum leptin levels. Multiple logistic regression analysis showed that the prenatal leptin levels were associated with depressive symptoms at 42 days postpartum (OR=0.026, P=0.001). Conclusion Prenatal serum leptin levels may be associated with postpartum depressive symptoms, and high levels of leptin are protective factors for postpartum depression.