Observational studies suggest an association between a low docosahexaenoic acid (DHA, 22:6n-3) status after pregnancy and the occurrence of postpartum depression. However, a comparison of the actual biochemical plasma DHA status among women with and without postpartum depression has not been reported yet. The contents of DHA and of its status indicator n-6 docosapentaenoic acid (n-6DPA, 22:5n-6) were measured in the plasma phospholipids of 112 women at delivery and 32 weeks postpartum. At this latter time point, the Edinburgh Postnatal Depression Scale (EPDS) questionnaire was completed to measure postpartum depression retrospectively. The EPDS cutoff score of 10 was used to define 'possibly depressed' (EPDS score > or =10) and non-depressed women (EPDS score <10). Odds ratios (OR) were calculated using a multiple logistic regression analysis with the EPDS cutoff score as dependent and fatty acid concentrations and ratio's as explanatory variables, while controlling for different covariables. The results demonstrated that the postpartum increase of the functional DHA status, expressed as the ratio DHA/n-6DPA, was significantly lower in the 'possibly depressed' group compared to the non-depressed group (2.34+/-5.56 versus 4.86+/-5.41, respectively; OR=0.88, P=0.03). Lactating women were not more predisposed than non-lactating women were to develop depressive symptoms. From this observation it seems that the availability of DHA in the postpartum period is less in women developing depressive symptoms. Although further studies are needed for confirmation, increasing the dietary DHA intake during pregnancy and postpartum, seems prudent.