The effect of n-3 long-chain PUFA (n-3 LCPUFA) on depression in healthy subjects is unclear, and most of the previous studies have focused on populations eating Western diets with lower fish intake. The present study investigated the association between blood levels of n-3 LCPUFA and depressive symptoms in Japanese community dwellers with higher n-3 LCPUFA blood levels. A cross-sectional study was conducted from 2006 to 2008, including 1050 men and 1073 women aged 40 years or older from the National Institute for Longevity Sciences – the Longitudinal Study of Aging. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to assess depressive symptoms. Multiple logistic regression analysis was performed to estimate the OR and 95 % CI for a CES-D score ≥16. Serum concentrations of n-3 PUFA, but not n-6 PUFA, were inversely associated with depressive symptoms. Compared with the lowest quintile, the adjusted OR for serum EPA at the fourth and fifth quintiles were 0·55 (95 % CI 0·35, 0·85) and 0·64 (95 % CI 0·42, 0·98), respectively, and at the fifth quintile for DHA it was 0·58 (95 % CI 0·37, 0·92), for the presence of depressive symptoms (P
for trend=0·013 and 0·011, respectively). Serum levels of EPA and DHA were inversely associated with depressive symptoms in Japanese community dwellers with higher blood levels of n-3 LCPUFA, suggesting that n-3 LCPUFA intakes corresponding to higher levels in a Japanese population may have implications for a lower prevalence of depression.