Objectives: This study aimed to examine the association of Per and Polyfluoroalkyl substances (PFAS) and markers of chronic inflammation and oxidative stress. Methods: Using data (n = 6652) from the National Health and Nutrition Examination Survey (NHANES) 2005–2012, generalized linear models were used to examine the association between PFAS and inflammatory (ferritin, alkaline phosphatase, C-reactive protein, absolute neutrophil count and lymphocyte count) and oxidative stress (serum bilirubin, albumin and iron) per unit exposure to PFAS while adjusting for covariates. Study participants were those ≥20 years of age. Outcome variables were markers of chronic inflammation and oxidative stress and exposure variables were PFAS. Resullts: Percentage change in Perfluorohexane sulfonic acid (PFHxS), Perfluorononanoic acid (PFNA), Perfluorooctanoic acid (PFOA), Perfluorooctane sulfonic acid (PFOS), and Perfluorodecanoic acid (PFDA) were all significantly associated with percentage increases in lymphocyte counts, beta (95% confidence interval); 0.04(0.02,0.05), 0.04(0.02,0.05), 0.05(0.03, 0.07), 0.04(0.03,0.05), 0.03(0.13,1.23) and with percentage increases in serum iron 0.07(0.05,0.09), 0.04(0.02,0.07), 0.10(0.07,0.12), 0.05(0.03,0.07), 0.04(0.02,0.06) and increased serum albumin 0.02(0.02,0.02), 0.02(0.02,0.03), 0.03(0.03,0.04), 0.02(0.017, 0.025), 0.01 (0.01, 0.05). Only PFHxS, PFNA, PFOA and PFOS were associated with percentage increases in serum total bilirubin 0.04(0.03,0.05), 0.02(0.00,0.03), 0.06(0.04,0.08), 0.03(0.02,0.05). Similar results were obtained for categorical quintile analysis with PFOA showing a significant trend (P < 0.001) with lymphocyte count, serum iron, serum total bilirubin and serum albumin. Trend for neutrophil count was not significant (p = 0.183). Conclusion: Per and Polyfluoroalkyl substances are associated with markers of chronic inflammation and oxidative stress. Increased exposure leads to increase in serum concentration of these markers meaning these chemicals are associated with both chronic inflammation and oxidative stress.