Background & aims:The metabolic syndrome (MetS) is a clustering of various metabolic abnormalitieswhich is associated with increased risk of cardiovascular disease (CVD) and type 2 diabetes mellitus. Dueto its increasing prevalence, it has become an important public health concern. Altered fatty acid (FA)composition and desaturase activities have been associated with several metabolic diseases, includingMetS. The aim of the present study was to evaluate the relationship of the plasma FA profile anddesaturase activities with the MetS in a Mediterranean population at high risk of CVD.Methods:Baseline data from 427 participants aged 55-80 years who took part in the interventional PREDIMED study were obtained. Individual FA was determined in plasma and desaturase activities wereestimated from product/precursor ratios. Odds ratios (OR) and partial correlation coefficients were usedto examine these relations with MetS and its components, respectively.Results:We found higher levels of C14:0, C16:0, C16:1n-7, estimatedD9- or stearoyl-CoA desaturase(SCD), and estimatedD6desaturase (D6D), and lower levels of C18:2n-6 in people with MetS compared tothose without it. After adjustment for several confounders, only higher quartiles of C14:0, C16:0, C16:1n-7, and D6D were found to be associated with an increasing prevalence of MetS, while higher quartiles ofC18:2n-6 were inversely associated with MetS. High proportions of C14:0, C16:0, C16:1n-7, C20:3n-6,SCD, and D6D, and decreased proportions of C18:2n-6 and estimatedD5-desaturase (D5D) were asso-ciated with adverse profiles of several metabolic risk factors. Women showed more unhealthy FA patternand lipid profiles than men, but only among those with MetS.