Weight gain is a commonly reported side effect of adjuvant chemotherapy. A change in resting energy expenditure during treatment has been a suggested mechanism for weight gain. We prospectively measured resting energy expenditure, weight change, and body composition (dual-energy x-ray absorptiometry) in 10 women undergoing adjuvant chemotherapy for breast cancer. There was no change in resting energy expenditure across cycles of chemotherapy (P =.78) or from baseline to the end of treatment (1,189.68 +/- 80.27 vs 1,205.76 +/- 56.71 kcal/d; P =.74). Overall, participants did not gain weight across treatment. However, there was an overall trend toward weight gain (66.3 +/- 5.1 vs 68.2 +/- 5.0 kg; P =.09), and participants did show an increase in total fat mass (24.2 +/- 3.8 vs 26.5 +/- 3.2 kg; P =.04), whereas muscle mass remained the same. Although no change in resting energy expenditure was seen, the observed increase in total fat mass is consistent with a decrease in physical activity level commonly reported with adjuvant chemotherapy treatment of breast cancer, and these body composition changes may have important health implications for survivors.