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BackgroundWith increased life expectancy, cognitive decline has emerged as a prevalent neurodegenerative disorder.ObjectiveThis study aimed to examine the correlation between concentrations of Plasma long-chain n-3 polyunsaturated fatty acids (LCPUFAs) and cognitive performance in elderly Americans.MethodsData were analyzed from older adults enrolled in two NHANES cycles. Participants completed four cognitive assessments, including the Immediate Recall Test (IRT), Delayed Recall Test (DRT), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Linear regression and restricted cubic spline modeling examined associations between plasma LCPUFAs levels and cognitive test outcomes.ResultsThe cohort included 610 adults aged 69 years on average, 300 (49.2%) males and 310 (50.8%) females. The median LCPUFAs concentration was 309.4 μmol/L, with an interquartile range of 244.7–418.9 μmol/L. In unadjusted and adjusted generalized linear regression model analyses, circulating LCPUFAs exhibited significant positive correlations with DRT performance. No relationships were detected among those with chronic conditions (chronic heart failure, stroke, diabetes). A significant association between LCPUFAs levels and DRT scores was evident in males but not females.ConclusionPlasma LCPUFAs concentrations were significantly associated with DRT performance in males free of chronic illnesses, including heart failure, stroke, and diabetes.