Objective: To examine the relationship between psychological distress (PD) and plasma n-3 long-chain (LC) PUFA, i.e. EPA, docosapentaenoic acid (DPAn-3) and DHA. Design: Population-based, cross-sectional Santé-Québec Health Survey (1991). Participants were categorized as high-level PD if they scored over the 80th percentile of the PD Index in the Santé-Québec Survey; non-distressed subjects were those who scored less than this cut-off. Associations between tertiles of n-3 fatty acids (FA) and the risk of high-level PD were expressed as odds ratios, with the lowest tertile as the reference group. Setting: Québec, Canada. Subjects: Data were analysed from a representative sample of 852 James Bay Cree Indian adults aged 18 years and over. Results: Proportions of n-3 FA were statistically significantly lower in the PD than in the non-distressed group. After adjustment for confounders, EPA was the only individual n-3 FA significantly associated with the risk of high-level PD. Combinations of EPA 1 DHA or EPA 1 DPAn-3 1 DHA or the sum of n-3 were also associated with the risk of high-level PD. Compared with the lowest tertile of EPA 1 DHA, the OR for high-level PD was 0?89 (95 % CI 0?59, 1?36) for the second and 0?56 (95 % CI 0?32, 0?98) for the third tertile, after controlling for confounders. Conclusions: In the present retrospective, cross-sectional study, we found that proportions of n-3 LC PUFA in plasma phospholipids, markers of n-3 LC PUFA consumption from fish, were inversely associated with PD.