The doubly labeled water method gives precise and accurate information on carbon dioxide production. Converting carbon dioxide production to energy expenditure needs information on the energy equivalent of CO2, which can be calculated with additional information on the substrate mixture being oxidized. One option is the calculation of the energy equivalent from the macronutrient composition of the diet. In energy balance, substrate intake and substrate utilization are assumed to be identical. In conclusion, doubly labeled water is an excellent method to measure energy expenditure in unrestrained humans in their normal surroundings over a time period of 1–4 weeks.