Per- and polyfluoroalkyl substances (PFAS) are a broad class of synthetic chemicals; some are present in most humans in developed countries. Several studies have shown associations between certain PFAS, such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), and reduced antibody concentration after vaccination against diseases such as Tetanus. Recent studies have reported associations between COVID-19 occurrence and exposure to certain types of PFAS. However, studies of antibody concentration after COVID-19 vaccination in relation to PFAS serum concentrations have not been reported. We examined COVID-19 antibody responses to vaccines and PFAS serum concentrations among employees and retirees from two 3M facilities, one of which historically manufactured PFOS, PFOA, and perfluorohexane sulfonic acid (PFHxS).Participants completed enrollment and follow-up study visits in the Spring of 2021, when vaccines were widely available. In total 415 participants with 757 observations were included in repeated measures analyses. Log-transformed concentrations of anti-spike IgG and neutralizing antibodies were modeled in relation to concentration of PFAS at enrollment after adjusting for antigenic stimulus group (9 groups determined by COVID-19 history and number and type of vaccination) and other variables. The fully adjusted IgG concentration was 3.45 percent lower (95% CI −7.03, 0.26) per 14.5 ng/mL (interquartile range) increase in PFOS; results for neutralizing antibody and PFOS were similar. For PFOA, PFHxS, and perfluorononanoic acid (PFNA), the results were comparable to those for PFOS, though of smaller magnitude. In our study data, the fully adjusted coefficients relating concentration of vaccine-induced antibodies to COVID-19 and interquartile range difference in serum concentration of PFOS, PFOA, PFHxS, and PFNA were inverse but small with confidence intervals that included zero. Our analysis showed that the coefficient for the four PFAS examined in detail was considerably affected by adjustment for antigenic stimulus group.