Background: A growing body of evidence suggests that deficits in long-chain omega-3 (LC. n-3) fatty acids may contribute to major depressive disorder (MDD) and principal causes of excess mortality including suicide and cardiovascular disease. In the present study we compared concentrations of docosahexaenoic acid (DHA, 22:6. n-3), the principal LC. n-3 fatty acid in brain, in the postmortem prefrontal cortex (BA10) of adult depressed suicide victims and controls with and/or without cardiovascular disease. Methods: DHA concentrations (μmol/g) in the prefrontal cortex (PFC, BA10) of adult male and female suicide victims (n=20) and controls with (n=8) or without (n=12) cardiovascular disease were determined by gas chromatography. Results: There was a non-significant trend for lower DHA concentrations in suicide victims compared with all controls (-10%, p=0.06, d=0.5). Significantly lower DHA concentrations were observed in suicide victims compared with controls without cardiovascular disease (-14%, p=0.03, d=0.7) but not controls with cardiovascular disease (-4%, p=0.71, d=0.1). There was a non-significant trend for lower DHA concentrations in controls with cardiovascular disease compared with controls without cardiovascular disease (-11%, p=0.1, d=0.6). Conclusions: Adult depressed suicide victims exhibit lower postmortem PFC DHA concentrations compared with controls without cardiovascular disease. These data add to a growing body of evidence implicating DHA deficits in the pathophysiology of MDD, suicide, and cardiovascular disease. © 2013 Elsevier Ltd.