Background: Postpartum depression is a serious health issue for new mothers and has negative consequences on both the mothers and the children and it constitutes a significant public health problem worldwide. Aim: To assess knowledge, attitudes and prevalence of postpartum depression among new mothers in Minia City. Design of the research: A descriptive cross-sectional research design. Setting: The research was carried out at vaccination clinics at primary health care centers located in Minia City, Egypt. Subjects: convenient sample of 290 new mothers who were within six months after giving birth and attended primary healthcare centers for vaccination of their babies were included. Tools: Tool I: A structured interview questionnaire (Socio Demographic Data and Obstetric history), Tool II: Structured questionnaire on new mothers' knowledge regarding postpartum depression, Tool III: Structured questionnaire on new mothers' attitudes towards postpartum depression, Tool IV: Edinburgh postnatal depression scale (EPDS). Results: This research revealed that (51%) of studied new mothers had a low level of knowledge regarding postpartum depression and (78.3%) of them had negative attitudes towards postpartum depression. The prevalence of postpartum depression was (56.2%) Conclusion: Poor knowledge and negative attitudes towards postpartum depression were widespread, and postpartum depression was an existing problem among the study population. Recommendations: Health education and screening for postpartum depression should be incorporated into the antenatal and postnatal care by governmental policies, as this will promote awareness and early recognition of postpartum depression.