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Background: Metabolic syndrome (MetS) is a set of conditions associated with an increased cardiovascular risk. Several serum fatty acids (FAs) seem to play an essential role in the development of cardiometabolic diseases and mortality. Thus, it is imperative to explore the impact of FAs on MetS parameters, using an early MetS screening tool such as MetScore, which is readily available in clinical practice. Aim: The aim of this study was to assess the potential correlation between serum FAs and cardiovascular risk using a MetScore. Methods: This cross-sectional study involved 41 women with severe obesity. The MetScore was calculated, and participants were categorized into high- and low-cardiovascular-risk groups based on the median MetScore value. Gas chromatography was used to quantify serum FAs. Generalized Linear Models were used to compare group means. The association was assessed through simple logistic regression, and an adjusted logistic regression was conducted to validate the association between Metscore and serum FAs. Results: The high-cardiovascular-risk group exhibited elevated values of HOMA-IR, palmitic, oleic, cis-vaccenic, and monounsaturated fatty acids, as well as the SCD-18C, indicating a heightened cardiovascular risk. Conversely, HDL-c, QUICK, gamma-linolenic, and eicosatetraenoic fatty acids showed lower values compared to the low-risk group. Conclusions: Women with severe obesity and high cardiovascular risk have lower values of some omega-3 and omega-6 FAs, considered cardioprotective and anti-inflammatory, and have higher lipogenic activity and FAs, correlated with high cardiovascular risk. These findings emphasize the need to address lipid metabolism in this population as a therapeutic target to reduce cardiovascular risk. Future research should explore clinical interventions that modulate fatty acid metabolism to mitigate cardiometabolic complications. Full article