Brown adipose tissue (BAT) contributes to whole-body energy expenditure (EE), especially cold-induced thermogenesis (CIT), in humans. Although it is known that EE and CIT vary seasonally, their relationship with BAT has not been investigated. In the present study, we examined the impact of BAT on seasonal variations of EE/CIT and thermal responses to cold exposure in a randomized crossover design. Forty-five healthy male volunteers participated, and their BAT was assessed by positron emission tomography and computed tomography. CIT, the difference of EE at 27ºC and after 2-h cold exposure at 19ºC, significantly increased in winter compared to summer, being greater in subjects with metabolically active BAT (High BAT, 185.6 kcal/d, 18.3 kcal/d, P<0.001) than those without (Low BAT, 90.6 kcal/d, -46.5 kcal/d, P<0.05). Multivariate regression analysis revealed a significant interaction effect between season and BAT on CIT (P<0.001). The cold-induced drop of tympanic temperature (Tty) and skin temperature (Tskin) in the forehead region and in the supraclavicular region close to BAT deposits were smaller in the High BAT group than in the Low BAT group in winter but not in summer. In contrast, the drop of Tskinin the subclavicular and peripheral regions distant from BAT was similar in the two groups in both seasons. In conclusion, CIT increased from summer to winter in a BAT-dependent manner, paralleling cold-induced changes in Tty/Tskin, indicating a role of BAT in seasonal changes in the thermogenic and thermal responses to cold exposure in humans.