IntroductionPuerto Rican adults report greater levels of depressive symptomatology compared to other Latino and non‐Latino groups. Dietary n‐3 fatty acid intake may improve symptoms of depression, but results are inconsistent. We examined the prospective relationship between biomarkers of n‐3 fatty acid consumption and depressive symptomatology.MethodsCohort (Boston Puerto Rican Health Study) of 1,067 participants with mean age 57 y (SD: 8) and 72.3% female. Degree of depressive symptomatology was obtained at baseline and 2 y (IQR 2.0‐2.2) using the Center for Epidemiology Studies Depression Scale (CES‐D). We measured red blood cell (RBC) membrane fatty acid composition at baseline. N‐3 fatty acid index was defined as the sum total of eicosapentaenoic and docosahexaenoic acid expressed as a percent of total RBC fatty acid content.ResultsIn multivariate models, n‐3 fatty acid index was inversely associated with 2 y CES‐D score , adjusting for baseline score [mean (95% CI); Q1 19.9 (18.6, 21.2) vs. Q4 18.3 (17.0, 19.6); P‐trend<0.05, Table Model 5]. Results remained consistent after accounting for saturated, trans‐, n‐6 polyunsaturated, or monounsaturated fatty acid content (P‐trend=0.03‐0.08) or excluding those who changed n‐3 supplementation from baseline (P‐trend<0.05).ConclusionUsing an objective measure of n‐3 fatty acid intake, our data suggest that n‐3 fatty acid consumption may be beneficial in the management of depressive symptomatology. Table. Prospective relationship between baseline n‐3 fatty acid index and CES‐D score at 2 y follow‐up (n=1067) Baseline n‐3 RBC fatty acid index Q1 3.1±0.5% Q2 4.0±0.2% Q3 4.7±0.2% Q4 6.0±0.9% n=266 n=267 n=267 n=267 Model Covariates mean (95%CI) mean (95%CI) mean (95%CI) mean (95%CI) P‐trend 1 baseline CES‐D score, anti‐depressive medication use, time between visits 20.4 (19.2, 21.6) 18.7 (17.5, 19.9) 17.7 (16.5, 18.9)* 17.7 (16.4, 18.9)* &lt;0.001 2 + sex, age, BMI, smoking status 20.0 (18.8, 21.3) 18.5 (17.3, 19.8) 17.8 (16.5, 19.1)* 18.2 (16.8, 19.5) &lt;0.05 3 + high school education status 20.0 (18.8, 21.3) 18.5 (17.3, 19.7) 17.8 (16.5, 19.1)* 18.2 (16.9, 19.6) &lt;0.05 4 + physical activity score 20.0 (18.8, 21.3) 18.5 (17.3, 19.7) 17.8 (16.5, 19.1)* 18.3 (17.0, 19.6) &lt;0.05 5 + Healthy Eating Index 2005 score excluding healthy oil component 19.9 (18.6, 21.2) 18.4 (17.1, 19.6) 17.7 (16.4, 19.0)† 18.3 (17.0, 19.6) &lt;0.05 †P=0.05 to &lt;0.1, *P&lt;0.05 compared to Q1