Background: Fatty acids (FA) have a role on energy storage and membrane formation. FA consists of an aliphatic chain with varying number of carbon and a carboxylic functional group. Perfluorooctanoic acid (PFOA) exhibits a similar structure to that of the FA. Given their structural resemblance, we hypothesized that alterations in FA metabolism could arise from competition with PFOA for endogenous FA binding sites in transport and with FA binding proteins. Objectives: Explore associations of serum concentrations of perfluorooctanoic acid (PFOA) with serum concentrations of linoleic (LA), eicosapentanoic (EPA), and docosapentanoic (DHA) acid in adults. Methods: We analyzed data from 1,829, 20-80 years old participants in the 2003–2004 National Health and Nutrition Examination Survey (NHANES). Linear regression models were used to estimate adjusted predicted means of the FA (in µmol/L) for quartiles of PFOA (in ng/mL) and explore linear trends. Results: Increasing concentrations of PFOA were not associated with adjusted predicted means of serum LA (Q1 3534, Q2 3445, Q3 3778, Q4 3399) (p trends=0.6460). Increasing concentrations of PFOA, however, were associated with increasing trends in adjusted predicted means of serum EPA (Q1 49.8, Q2 51.5, Q3 60.9, Q4 55.7).