Weight gain has been reported in early stage breast cancer patients during chemotherapy, but the involved mechanisms remain unclear. A chemotherapy-induced decrease of brown adipose tissue (BAT) activity may partly contribute to weight gain in these patients. A positron emission tomography/computed tomography scan was performed at baseline and after 1 course of docetaxel + trastuzumab treatment in 26 breast cancer women. Variation of the maximal standardized uptake value of BAT in the cervical and supraclavicular regions between the 2 measures was assessed according to weight changes. Overall, (18)F-FDG uptakes in BAT decreased by 11.3% after 1 course of chemotherapy (p = 0.03). No correlation was found between the baseline values of (18)F-FDG uptake and body mass index or age of patients, but as expected (18)F-FDG uptake was dependent on season period. Among the patients, 35% gained weight, 25% lost weight, and 40% remained stable. Women who gained weight during chemotherapy experienced a significant decrease of (18)F-FDG uptake in BAT (p = 0.005). Decreased activity of BAT was associated with body weight gain during chemotherapy. These original data suggest for the first time that BAT modulation by chemotherapy would be a potential contributor to body weight gain through blunted thermogenesis in breast cancer patients.