Polyfluoroalkyl substances (PFAS) are synthetic compounds shown to be associated with metabolic disturbances in the experimental literature. Evidence of the relationship between PFAS and MetS from human epidemiological studies remains inconclusive and warrants further study. This study leverages a pooled index to examine associations between a mixture of PFAS and metabolic syndrome in a sample of adults in the United States. Using data from the National Health and Nutrition Examination Survey 2005-2018 (n= 8095), we examined the relationship between serum concentrations of perfluorohexanesulfonic acid, perfluorononanoic acid, perfluorodecanoic acid, perfluoroundecanoic acid and 2-(N-Methyl-perfluorooctane sulfonamido acetic acid, and MetS. We evaluate individual associations with logistic regression and joint associations in a pooled index (PI) model. One standard deviation increase in the PI was associated with 18% decrease in odds of MetS (OR: 0.82, 95% CI: 0.76, 0.89). In logistic regression models, higher PFAS concentrations were also associated with decreased odds of MetS in perfluorodecanoic acid (PFDA) (OR: 0.43, 95% CI: 0.28, 0.64) and perfluoroundecanoic acid (PFUA) (OR: 0.19, 95% CI: 0.11, 0.36). This study found an inverse association between serum PFAS concentration and MetS, in both pooled and individual models; however, given the cross-sectional design, these findings should be interpreted cautiously.