ABSTRACT: Background: Postpartum depression is a serious condition for women after childbirth. Although its etiology is unclear, one potentially important predictive variable that has received little attention is maternal sleep deprivation. The objective of this study was to examine relationships among infant sleep patterns, maternal fatigue, and the development of postpartum depression in women with no major depressive symptomatology at 1 week postpartum. Methods: As part of a population-based postpartum depression study, 505 women who had an Edinburgh Postnatal Depression Scale (EPDS) score < 13 at 1 week postpartum completed questionnaires at 4 and 8 weeks postpartum. Results: Mothers exhibiting major depressive symptomatology (EPDS > 12) at 4 and 8 weeks were significantly more likely to report that their baby cried often, be woken up 3 times or more between 10 pm and 6 am, have received less than 6 hours of sleep in a 24-hour period over the past week, indicate that their baby did not sleep well, and think that their baby's sleep pattern did not allow them to get a reasonable amount of sleep. Consistent with these findings, mothers with an EPDS score > 12 were significantly more likely to respond that they often felt tired. Conclusions: These results suggest that infant sleep patterns and maternal fatigue are strongly associated with a new onset of depressive symptoms in the postpartum period, and provide support for the development of postpartum depression preventive interventions designed to reduce sleep deprivation in the early weeks postpartum.