Background: Concurrent chemoradiation (CTRT) improves outcomes in oropharyngeal cancer (OPC) but causes toxicities that alter body composition. In other cancers, loss of lean body mass (sarcopenia) is associated with poor prognosis. Changes in body composition in OPC, and the clinical importance of these alterations, have not been studied. Methods: Using a retrospective design, 234 OPC patients (mean age, 58 years (range 27 to 83); mean BMI, 29 kg/m²) receiving definitive CTRT were studied. Skeletal muscle cross-sectional area (CSA) at the third lumbar vertebra (L3) and thigh were assessed by CT-scan prior to and after completion of CTRT (median: 13.5 wks; range 2-27) and normalized to stature to obtain skeletal muscle index (cm²/m²). Sarcopenia was defined using previously published cutoffs. Cox models were used to assess the relationship between sarcopenia and recurrence-free survival (RFS) and overall survival (OS). Wilcoxon rank-sum tests were used to assess changes in percent loss in weight and L3 and thigh muscle CSA in patients hospitalized post-CTRT. Results: Prior to CTRT, 68% of patients were classified as sarcopenic. HPV-testing was completed in 168 (72%); 149 were positive. Post-CTRT, body mass (kg) decreased a median of 13.8% (IQR: 10.1% to 18.7%, p < .001) while muscle CSA at L3 and thigh decreased by 11.2% (IQR: 6.9% to 16.8%, p < .001) and 13.6% (IQR: 5.5% to 21.2%, p < .001), respectively; 89% were classified as sarcopenic. Older age and male were significant baseline predictors of sarcopenia post-CTRT (p’s < 0.05). Fifty-eight (25%) patients were hospitalized within 3 months of CTRT. Median follow-up was 34 months; in this period, 26 recurrences and 19 deaths were observed. Greater percent weight loss and thigh muscle CSA loss were positively associated with risk of hospitalization (p’s < 0.01); baseline or post-treatment sarcopenia were not associated with RFS or OS (p’s > 0.05). Conclusions: A significant proportion of OPC patients present with clinical sarcopenia, while CTRT increases the proportion of subjects with this condition.Decreases in body and muscle mass are associated with hospitalization. The long-term clinical impact of these losses remains to be determined.