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Background: Per- and polyfluoroalkyl substances (PFAS) may alter body composition by lowering anabolic hormones and increasing inflammation. Prior studies have shown inconsistent associations between PFAS exposure and fat mass; none have examined lean (i.e., muscle) mass, and there has been limited longitudinal investigation in children. Methods: We studied 426 children in the Boston-area Project Viva cohort. We examined associations of plasma concentrations of six PFAS in mid-childhood [median age 7.6 years; 2006-2010] with change in height-adjusted indices of body composition measured by dual-energy X-ray absorptiometry in mid-childhood and early adolescence [median age 12.8 years]. We used linear regression models adjusted for sociodemographics, breastfeeding duration, and other perinatal and child characteristics. We examined effect modification by sex. Results: Plasma concentrations were highest for perfluorooctane sulfonate (PFOS) [median (IQR) 6.5 (5.9) ng/mL]. Median (IQR) change in lean mass index was 1.7 (1.6) kg/m², change in total fat mass index was 1.4 (2.2) kg/m², and change in truncal fat mass index was 0.6 (1.0) kg/m² from mid-childhood to early adolescence. Greater plasma concentrations of PFOS, perfluorooctanoate, and perfluorodecanoate were associated with less gain in lean mass index [e.g., -0.27 (95% CI: -0.42, -0.11) kg/m² for each doubling of PFOS] from mid-childhood to early adolescence. Among girls only, greater plasma concentrations of PFOS were associated with less gain in total and truncal fat mass indices [e.g., change in truncal fat mass index was -0.20 (95% CI: -0.34, -0.05) kg/m² for each doubling of PFOS; p_int=0.04]. Conclusion: In a large prospective US cohort, children with greater plasma concentrations of several PFAS had less gain in lean mass through early adolescence. This finding is important in light of emerging evidence suggesting that adolescents with lower muscle mass and strength may have adverse cardiometabolic health.