Objective: The risk factors for postnatal depressive symptoms (PNDS) are numerous, but little is known about the protective factors or the interactions between different exposures. The present study explored the pathways between maternal, infant and parenthood vulnerabilities or risk/protective factors and PNDS at 2 months postpartum (PP) in a large sample of women from the general population. Methods: We used data from the French ELFE cohort, a nationally representative cohort of children followed-up from birth. The available information about vulnerabilities or risk/protective factors for PNDS was collected during the maternity ward stay (mother or medical records) and at 2 months PP (mother by phone). PNDS were evaluated with the Edinburgh Postnatal Depression Scale (EPDS) at 2 months. A measurement model was built based on the psychosocial model for PNDS of Milgrom and colleagues using exploratory factor analysis. The Structural Equation Model was used to investigate the pathways between vulnerability, risk/protective factors and PNDS at 2 months PP. Results: In the study sample (n= 11,583), a lack of a partner’s perceived antenatal emotional support, consultation with a mental health specialist before pregnancy, family financial difficulties, prenatal psychological distress and a difficult pregnancy experience were directly associated with the severity of maternal PNDS at 2 months PP, as well as lack of perceived postnatal support. Family financial difficulties and consultation with a mental health specialist before pregnancy were also indirectly associated with the intensity of PNDS through a lack of perceived antenatal emotional support, a difficult pregnancy experience, prenatal psychological distress and a lack of perceived postnatal support. Regarding infant and parenthood characteristics, infant self-regulation difficulties, maternal difficulty in understanding infant crying and infant hospitalisation were directly associated with PNDS severity at 2 months PP, while maternal difficulty in understanding an infant’s cries was also indirectly associated with infant self-regulation difficulties. Conclusions: Perinatal professional support should begin antenatally and target the couple’s prenatal functioning, with particular attention to women presenting a history of psychiatric disorders, especially those of low socioeconomic status. After delivery, addressing infant and parenthood characteristics is also recommended.