Postpartum depression (PPD) is a major cause of burden of diseases in women within the first 4 weeks of delivery. The aim of this study was to determine the prevalence and the role of various factors in PPD in the northern and northeastern regions of Khuzestan province. Methods: This descriptive-analytical study was undertaken as the first phase of a case-control study on 1424 mothers in the first 24 to 48 hours after childbirth between January 2019 and January 2020. The data collected covered

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... hree areas: baseline characteristics, medical history, and PPD. The latter was measured using the Edinburgh Postpartum Depression Scale with a cut-off point of equal to or greater than 12. The collected data were analyzed using Stata-16 software and simple and multiple Logistic Regression models. Results: The prevalence of PPD was estimated at 26.6% in the study sample. In the multiple model, the History of elective abortion (OR= 2.26, 95%CI=1.19, 4.27), delivery in the summer (OR= 2.11,95%CI=1.39, 3.20), birth defect (OR= 2.09, 95%CI=1.10, 3.94), the history of infertility treatment (OR= 0.33, 95CI=0.18, 0.61) and living in urban areas (OR= 0.52, 95%CI=0.39, 0.70), had relationship with the chance of developing PPD. Conclusion: The results of this study, which sought to identify factors reinforcing and preventing PPD, can be used to identify mothers at risk for PPD. Moreover, it can help make appropriate interventions, including psychological and emotional support of mother during and even before pregnancy to alleviate PPD.