Objective: We measured the association between early breastfeeding experience and maternal mood at two months postpartum. Methods: We used logistic regression to evaluate the association between early breastfeeding experience and maternal mood, quantified with the Edinburgh Postnatal Depression Scale (EPDS), among women who initiated breastfeeding in the Infant Feeding Practices Survey II. Women reported their early breastfeeding experiences at 1 month, and they completed the EPDS at 2 months. Results: In the neonatal period, 2586 women reported ever breastfeeding, among whom 223 (8.6%) met criteria for major depression (EPDS ≥13) at 2 months postpartum. Women who reported disliking breastfeeding in the first week were more likely to meet criteria for major depression at 2 months (OR 1.42, 95% CI 1.04-1.93), adjusting for maternal age, parity, education, ethnicity, and postnatal WIC participation. We also found that women who were depressed were more likely to report severe breastfeeding pain in the first day (adjusted OR 1.96, 95% CI 1.17-3.29, vs. no pain), the first week, (adjusted OR 2.13, 95% CI 0.74-6.15, vs no pain), and in the second week (adjusted OR 2.24, 95% CI 1.18-4.26, vs. no pain). Conclusions: Women who disliked breastfeeding or experienced severe pain in the neonatal period were more likely to have depressive symptoms at 2 months postpartum. Early breastfeeding difficulties may identify a subgroup of women at high risk for postpartum depression.