High fish consumption and omega-3 polyunsaturated fatty acid (PUFA) intake are suggested to benefit mental well-being but the current evidence is conflicting. Our aim was to evaluate whether a higher level of fish consumption, a higher intake of omega-3 PUFAs, and a higher serum concentration of omega-3 PUFAs link to a lower 12-month prevalence of depressive episodes.We used data from the nationwide Health 2000 Survey (n = 5492) and the Fishermen Study on Finnish professional fishermen and their family members (n = 1265). Data were based on questionnaires, interviews, health examinations, and blood samples. Depressive episodes were assessed with the M-CIDI (the Munich version of the Composite International Diagnostic Interview) and a self-report of two CIDI probe questions, respectively. Fish consumption was measured by a food frequency questionnaire (g/day) and independent frequency questions (times/month). Dietary intake (g/day) and serum concentrations (% from fatty acids) of PUFAs were determined. Fish consumption was associated with prevalence of depressive episodes in men but not in women. The prevalence of depressive episodes decreased from 9% to 5% across the quartiles of fish consumption (g/day) in men of the Health 2000 Survey (p for linear trend = 0.01), and from17% to 3% across the quartiles of fish consumption (times/month) in men of the Fishermen Study (p for linear trend = 0.05). This association was modified by lifestyle; in the Health 2000 Survey a higher level of fish consumption was related to a lower prevalence of depressive episodes in men who consumed the most alcohol, were occasional or former smokers, or had intermediate physical activity. The associations between depressive episodes and the intake or serum concentrations of omega-3 PUFAs were not consistent.In men, fish consumption appears as a surrogate for underlying but unidentified lifestyle factors that protect against depression.