Per-and polyfluoroalkyl substances (PFAS) exposure has been associated with reduced antibody levels. Higher red blood cell (RBC) folate was previously associated with lower serum PFAS concentrations in adolescents. This study included 819 adolescents aged 12−19 years who had detectable rubella and measles antibody levels in serum from the U.S. National Health and Nutrition Examination Survey 2003−2004 and 2009−2010 cycles.We found inverse associations between serum PFOS and PFHxS and rubella antibodies, between PFOA and mumps antibodies, and between PFAS mixtures and rubella and mumps antibodies, only among adolescents with RBC folate concentrations <66th percentile (lower folate group) while not among adolescents with higher RBC folate levels (upper folate group). Specifically, per quartile increase in serum concentrations of the total PFAS mixture was associated with a 9.84% (95% CI: −15.57%, −3.74%) decrease in rubella antibody and an 8.79% (95% CI: −14.39%, −2.82%) decrease in the mumps antibody concentrations only in the lower folate group, while null associations were found for the upper folate group. If confirmed in mechanistic studies or prospective epidemiologic studies, these findings may have important implications for using folate as a mitigation measure against immunerelated PFAS effects.