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Background: Women with antenatal depression often have a higher risk of developing postpartum depression (PPD) after delivery. A number of factors associated with the PDD in those previously reporting antenatal depression have been suggested, but further research is needed. This study aimed to investigate factors associated with developing subsequent postnatal depression in women who had screened positive for antenatal depression. Methods: This study was carried out in Hangzhou women's Hospital. 578 women who experienced antenatal depression from this cohort were enrolled in this study. The sociodemographic and clinical characteristics of the participants were collected and tabulated against the incidence of postnatal depression. Binary logistic regression was used to estimate the effects of the principal underlying variables. The Chinese-version Edinburgh Postnatal Depression Scale (EPDS) was used to screen for PPD. Antenatal screening for depression was conducted at 28–34 weeks during pregnancy and postpartum depressive symptoms were assessed at 6 weeks after childbirth in the women. Path Analysis of Structural Equation Model (SEM) was employed to explore the direct, indirect, and total effects of risk factors of PPD. Results: 57.6% (n = 333) of the participants subsequently developed PPD in our study. The results of the logistic analysis indicated that ages ≤ 35 years old (OR = 1.852; 95%CI: 1.002–3.423), non-one-child families (OR = 1.518; 95%CI: 1.047-2.200), and rare care from partner during pregnancy (OR = 2.801; 95%CI: 1.038–7.562), the antenatal EPDS score (OR = 1.128; 95%CI: 1.052–1.209), pyrexia during pregnancy (OR = 2.43; 95%CI: 1.358–4.345), fairly good (OR = 1.836; 95%CI: 1.009–3.340), fairly bad (OR = 3.919; 95%CI:2.072–7.414) and very bad postpartum sleep quality (OR = 9.18; 95%CI: 2.335–36.241) were associated with increased risk of PPD (compared to very good postpartum sleep quality). In path analysis model, antenatal EPDS score (standardized total β = 0.173) and pyrexia during pregnancy (standardized total β = 0.132) had both direct and indirect effects (the impact on outcome variables needs to be determined through other variables) on PPD. Sleep quality after delivery (standardized β = 0.226) and one-child family (standardized β = 0.088) had direct effects only on PPD. Conclusion: The results from our study indicated that more than 50% of the women who experienced antepartum depression would subsequently develop PPD. Depressive symptoms and pyrexia during pregnancy increase PPD scores, and these effects were in part mediated via poor sleep quality during the postpartum period. [ABSTRACT FROM AUTHOR]