Background: The relationship between breastfeeding and postpartum depression is bidirectional. Breastfeeding improves the maternal and neonatal health. There is now growing evidence that it might play a role in the prevention of postpartum depression. Objective: This study explores the relationship between breastfeeding and maternal postpartum depression. It also estimates the prevalence rate of postpartum depression among Saudi women. Methods: This is a cross-sectional study. Three-hundred postpartum women were recruited for this study from various hospitals in the Eastern Province of Saudi Arabia. Likelihood of depression was assessed using the Edinburgh Postpartum Depression Scale (EPDS). Socio-demographic data were collected as well as data regarding breastfeeding duration and intention to breastfeed. Data analysis was done using SPSS version 21, using parametric tests; independent t-test and One-Way ANOVA. Results: Postpartum mothers who intended to breast-feed their babies had a lower EPDS scores compared with those who did not intend to breast-feed. No correlation was found between the duration of breastfeeding and EPDS scores. Prevalence rate of postpartum depression in our sample was 14%. Greater age, having previous babies, intention to breastfeed and vaginal delivery were significantly associated with actual breastfeeding. Conclusion: Screening for mothers in the early postpartum period is essential to detect those who are at risk for postpartum depression. Breastfeeding may help to reduce and prevent the appearance of symptoms of depression. Prevalence rate of postpartum depression in Saudi Arabia, 14%, is similar to the worldwide rate.