Postpartum depression and depressive symptoms have a major impact on maternal and infant health and wellbeing, yet to date their aetiology remains unclear. One hypothesis suggests a link between these symptoms and variations in prenatal cortisol levels, but existing evidence is limited and inconclusive. This study aims to provide additional evidence to disentangle the relationship between prenatal cortisol concentrations and subsequent occurrence of postpartum depressive symptoms. Cortisol for all three trimesters of pregnancy was extracted from the hair of 775 women participating in the French ELFE cohort. Depressive symptomatology at two months postpartum was assessed through the Edinburgh Postpartum Depression Scale (EPDS). Associations between prenatal cortisol levels and EPDS scores were tested using propensity-score weighted logistic regression models to control for confounders. An increase in mean cortisol concentrations was observed from the first to the third trimester of pregnancy.No significant differences in hair cortisol concentrations were found during the first and second trimesters between women who experienced postpartum depressive symptoms and those who did not. However, an association was observed between third trimester hair cortisol concentrations and depressive symptoms at two months postpartum. Women whose cortisol concentrations fell within the second quartile had a higher risk of subsequent PPDS (aOR = 2.67, 95%CI [1.01, 7.08]).Using a large sample from the general population, we observed an association between hair cortisol levels during the third trimester of pregnancy and postpartum depressive symptoms. Nevertheless, our results suggest that future studies could benefit from investigating other biomarkers of the reactivity of the corticotropic axis.Read less <