Background: Mothers selectively transfer docosahexaenoic acid (DHA) to their fetuses to support optimal neurological development during pregnancy. Without sufficient dietary intake, mothers become depleted of DHA and may increase their risk of suffering major depressive symptoms in the postpartum period. We postulated that the DHA content of mothers’ milk and seafood consumption would both predict prevalence rates of postpartum depression across countries. Methods: Published prevalence data for postpartum depression were included that used the Edinburgh Postpartum Depression Scale ( n=14 532 subjects in 41 studies). These data were compared to the DHA, eicosapentaenoic acid (EPA) and arachidonic acid (AA) content in mothers’ milk and to seafood consumption rates in published reports from 23 countries. Results: Higher concentrations of DHA in mothers’ milk ( r=−0.84, p<0.0001, n=16 countries) and greater seafood consumption ( r=−0.81, p<0.0001, n=22 countries) both predicted lower prevalence rates of postpartum depression in simple and logarithmic models, respectively. The AA and EPA content of mothers’ milk were unrelated to postpartum depression prevalence. Limitations: These findings do not prove that higher omega-3 status cause lower prevalence rates of postpartum depression. Data on potentially confounding factors were not uniformly available for all countries. Conclusions: Both lower DHA content in mothers’ milk and lower seafood consumption were associated with higher rates of postpartum depression. These results do not appear to be an artifact of cross-national differences in well-established risk factors for postpartum depression. Interventional studies are needed to determine if omega-3 fatty acids can reduce major postpartum depressive symptoms.