Objectives: The burden of postpartum depression (PPD) is significant because it remains unrecognized, and it not only affects the mother adversely but also has a negative consequence on the family life and the development of the infant. The aim of the study was to measure the prevalence of PPD and identify the risk factors of PPD among mothers attending the well-baby clinic of six Primary Health Care centers in Abha city, Southwest Saudi Arabia. Materials and Methods: A total of 228 Saudi women having a child aged between two weeks to one year were recruited in the study by using a consecutive sampling technique. The Arabic version of the Edinburgh Postnatal Depression Scale (EPDS) was used as a screening tool to measure the prevalence of PPD. The mothers were also inquired about their socio-demographic characteristics and risk factors. Results: The prevalence rate of postpartum depression was 43.4%. Family conflict, and lack of support by spouse and family during pregnancy were found to be the strongest predictors of developing PPD. Women who had reported family conflict were at six times higher risk for developing PPD compared to those who did not have a family conflict (aOR = 6.5, 95% CI = 2.3–18.4). Women who reported a lack of spousal support during pregnancy encountered 2.3 fold increased risk for PPD (aOR = 2.3, 95% CI = 1.0–4.8) and women who had not received family support during pregnancy period were more than three times (aOR = 3.5, 95 % CI 1.6–7.7) likely to experience PPD. Conclusion: The risk of PPD among Saudi postnatal women was high. PPD screening should be an integral part of postnatal care. Awareness of women, spouses and families about potential risk factors can be a preventive strategy. The early identification of high-risk women during the antenatal and post-natal period could help to prevent this condition.