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Docosahexaenoic acid (DHA) shows anti-inflammatory/proresolution effects in the brain. Higher red blood cell (RBC) DHA in humans is associated with improved cognitive performance and a lower risk for suicide. Here, we hypothesized that binding to the 18 kDa translocator protein (TSPO), a proxy for microglia levels, will be higher in individuals with low DHA relative to high DHA levels. We also postulated that higher TSPO would predict poor cognitive performance and impaired stress resilience.RBC DHA screening was performed in 320 healthy males. [sup11/supC]PBR28 positron emission tomography was used to measure binding to TSPO in 38 and 32 males in the lowest and highest RBC DHA quartiles. Volumes of distribution expressed relative to total plasma ligand concentration (VsubT/sub) was derived using an arterial input function-based kinetic analysis in 14 brain regions.[sup11/supC]PBR28 VsubT/subwas significantly lower (by 12% and 20% in C/T and C/C rs6971 genotypes) in males with low RBC DHA than in males with high RBC DHA. Regional VsubT/subwas correlated positively and negatively with RBC DHA and serum triglycerides, respectively. No relationships between VsubT/suband cognitive performance or stress resilience measures were present.Contrary to our hypothesis, we found lower TSPO binding in low-DHA than in high-DHA subjects. It is unclear as to whether low TSPO binding reflects differences in microglia levels and/or triglyceride metabolism in this study. Future studies with specific targets are necessary to confirm the effect of DHA on microglia. These results underscore the need to consider lipid parameters as a factor when interpreting TSPO positron emission tomography clinical findings.