Marine omega-3 (n-3) fatty acid eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids have been associated with beneficial effects in mental health. Cultural and social changes have been related to a decline in mental health of the Inuit, but the role of diet has received scant attention. We examined the relationship between psychological distress (PD) and plasma n-3 among 368 Nunavik Inuit aged 18-74 years who took part in a survey in 1992. Participants were categorized as high-level PD if they scored over the 80th percentile of the PD Index Santé-Québec Survey (PDISQS-14), and non-distressed subjects were those who scored less than this cutoff. Compared with the non-distressed group, n-3 concentrations in the PD group were significantly lower in women but not in men. Compared with the lowest tertile of EPA + DHA, the odds ratios for high-level PD among women were 0.32 (95% CI: 0.13-0.82) for the second, and 0.30 (95% CI: 0.10-0.90) for the third tertile, after controlling for confounders. In males, there were no significant associations between EPA+DHA and PDISQS-14 scores. Our findings suggest that marine n-3 may play a role in PD among Inuit women. The gender difference observed in our analysis must be examined more carefully in future studies.