Depression is associated with an increased risk of cardiovascular disease, but the association with dietary habits is not well understood. The aim of this work was to statistically model the association of depressive symptoms with fatty acids intake in persons free of cardiovascular disease.A random multistage sampling, stratified by gender and age, was performed during 2001-2002. In the present work, psychological and dietary data from 453 men (19-89 years) and 400 women (18-84 years) were analyzed. Depression was assessed with the Zung's Self-rating Depression Scale (ZDRS). After a validation for the investigated population, plasma fatty acids in the form of their methyl esters were determined by gas chromatography, while dietary fatty acids were determined through a semiquantitative food frequency questionnaire and local food composition tables.Women had significantly higher scores on the ZDRS as compared with men (47 ± 9 vs. 43 ± 10, p < 0.001). Multiadjusted data analysis after adjusting for age, gender, lifestyle, and dietary habits revealed that increased polyunsaturated fatty acid (PUFA) and monounsaturated fatty acid (MUFA) concentrations, and, more specifically, high concentrations of plasma total n-3 fatty acids (b ± SE: -1.9 ± 0.5, p = 0.03), docosahexaenoic acid (-2.91 ± 1.04, p = 0.02), eicosapentaenoic acid (-2.54 ± 0.84, p = 0.03), α-linoleic acid (-16.8 ± 7.3, p = 0.01), and linoleic acid (-3.97 ± 0.21, p = 0.03), were associated with lower scores in the depression scale used.These results indicate that increased PUFA and MUFA concentrations are associated with diminished depressive symptomatology among apparently healthy adults.