Context: Adaptive thermogenesis is defined as the increase in energy expenditure in response to overfeeding or cold. Large inter-individual differences in adaptive thermogenesis have been described. Objective: Since there are indications for a common underlying mechanism, we studied in humans whether the increase in thermogenesis during short term overfeeding (3 days) is related to mild cold induced thermogenesis. Interventions: Therefore, 13 lean male subjects have been exposed to three experimental conditions in respiration chambers: baseline (36 hours in energy balance at thermoneutrality, 22 degrees C); overfeeding (84 hours 160% of energy balance, 22 degrees C); mild cold (84 hours in energy balance, 16 degrees C). Main outcome measures: During the interventions, total daily energy expenditure (TDEE), physical activity, skin temperatures, and core temperature were measured. After each condition, fasting plasma norepinephrine concentration was measured. Results: Overfeeding caused significant increases in TDEE (0.77 MJ/day, p<0.001). During cold exposure TDEE increased significantly (0.59 MJ/day, p<0.005), while physical activity decreased. The changes in TDEE during both overfeeding and mild cold exposure showed considerable inter-individual variation (respectively -0.11 to 1.61 MJ/day and -0.19 to 1.58 MJ/day). The individual changes in energy expenditure during mild cold exposure and overfeeding were highly correlated (p<0.005). Fasting norepinephrine plasma concentrations correlated significantly to energy expenditure in both situations (p<0.05). Conclusions: These results suggest that both overfeeding induced and mild cold induced adaptive thermogenesis share common regulating mechanisms. This indicates that cold exposure could be used as a biomarker for the individual thermogenic response to excess energy intake.