Per- and polyfluoroalkyl substances (PFAS) are a class of persistent chemicals used as industrial surfactants, fire-fighting foams, and textile treatments. Early childhood exposure to perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS) may affect the immune system to increase the risk of allergic and respiratory diseases. However, there are substantial gaps in our knowledge about the relationship between PFAS and immune-mediated outcomes such as asthma in children. Thus, we examined the cross-sectional associations of serum PFOA, PFOS, PFNA, and PFHxS concentrations with childhood asthma. We used data from children aged 3-11 years who participated in the National Health and Nutrition Examination Survey (2013-2014). Serum PFAS concentrations were measured in serum using analytical chemistry methods. Asthma was assessed by parent-reported, doctor-diagnosed, asthma using a standardized questionnaire. Controlling for covariates, we estimated odds ratios for asthma per standard deviation increase in ln-transformed serum PFAS concentrations (n = 607). We also examined effect measure modification by child age, sex, and race/ethnicity. PFOA (1.1; 95% CI: 0.8, 1.4), PFOS (1.2; 95% CI: 0.8, 1.7), PFNA (1.1; 95% CI: 0.8, 1.6), and PFHxS (1.1; 95% CI: 0.9, 1.6) were weakly associated with an increased odds of asthma. Age modified associations between serum PFOS, but not other serum PFAS concentrations, and odds of asthma (age x PFOS interaction term p-value = 0.03). Sex and race/ethnicity did not modify these associations. We observed some evidence that serum PFAS concentrations are weakly associated with increased asthma prevalence in US children.Copyright © 2020 Elsevier GmbH. All rights reserved.