The purpose of this study is to determine the prevalence and associated factors of postpartum depression among mothers in Nifas Silk Lafto Sub City, Woreda 1 and 2 health centers. Participants were recruited from the postnatal clinic at Nifas Silk Lafto Sub City, Woreda 1 and 2 health centers. Eligible participants were approached and requested to consent voluntarily to participate in this study. Data was collected using a structured questionnaire and analyzed using SPSS version 20.0 software. A total of 300 postnatal mothers were recruited in this study but 295 were analyzed. This study found a prevalence of postpartum depression at 45th day since delivery at 27.8% using K-10 score. 34% of the postnatal mothers were aged between 26-32 years. 82% were married and 27.8% were high school complete. 78% were not in any form of employment. 39.8% were primigravida or first time mothers.33.6% pregnancy was unplanned. Unemployment (r=0.8,P< 0.001), parity (r=0.7,P< 0.01), Income (r=0.7,P< 0.0001) and social support (r=0.7,P< 0.001) were statistically significantly associated with Postpartum Depression. No significant statistical association between Infant sex (r=0.48,P