Human biomonitoring studies have shown that concentrations of perfluorooctane sulfonic acid (PFOS) in men are higher than in women. We investigate sex differences in elimination of PFOS by fitting a population-based pharmacokinetic model to six cross-sectional data sets from 1999 to 2012 from the US National Health and Nutrition Examination Survey (NHANES) and derive human first-order elimination rate constants (kE) and corresponding elimination half-lives (t1/2) for PFOS, where t1/2 = ln 2/kE. We use a modified version of the Ritter population-based pharmacokinetic model and derive elimination rate constants separately for men and women. The model accounts for population-average lifetime changes in PFOS intake, body weight, and menstruation rate. We compare the model-derived elimination rate constant for hypothetical nonmenstruating women to the elimination rate constant for men and women when menstruation is included as a loss process to evaluate the hypothesis that loss of PFOS by menstruation is an important process for women. The modeled elimination half-life for men is 4.7 years, and the modeled elimination half-life for women when excluding losses from menstruation is 3.7 years. The elimination half-life for women when menstruation is included in the model is 4.0 years. Thus, menstruation accounts for 30% of the discrepancy in elimination of PFOS between men and women. The remaining discrepancy is likely due to other sex-specific elimination routes that are not considered in our modeling.