Cold exposure (CE) has been shown to enhance energy expenditure by activating brown adipose tissue thermogenesis and metabolism in humans. However, it remains to be elucidated if there are gender-specific differences in cold-induced thermogenesis and metabolism.To study the impact of mild CE on resting energy expenditure (REE) and metabolism in males compared to females.A cross-sectional study.117 healthy young Caucasians participated in this study (58 males). Mean age was 25.1 3.6 years and mean BMI 22.3 1.7 kg/m.Participants underwent a short-term CE using water perfused mattresses to activate non-shivering thermogenesis.REE was assessed before and 2 hours after CE followed by blood sampling. Selected metabolites and hormones were measured. Skin temperatures were monitored at various sites throughout the experiment.Participants showed a significant increase in REE after CE (6.5%, p<0.001). This increase did not differ between genders (p=0.908). However, there were differences between males and females in changes of plasma glucose (-5.1% vs. -7.4%, p=0.024), leptin (-14.3% vs. -30.1%, p<0.001) and adiponectin (5.4% vs. 12.8%, p=0.018) after CE. We observed a significant decrease of the supraclavicular skin temperature in men (-0.3%, p=0.034), but not in women (0.3%, p=0.326)(p=0.019 between genders).We did not observe a difference in the thermogenic response, measured as change of REE, to CE in women compared to men. However, we found that some metabolic and hormonal changes were more pronounced in women compared to men suggesting a gender-specific response to cold.