Faced with reduced levels of food, animals must adjust to the consequences of the shortfall in energy. We explored how C57BL/6 mice withdrew energy from different body tissues during three months of food restriction at graded levels up to 40% (calorie restriction: CR). We compared this to the response to equivalent levels of protein restriction (PR) without a shortfall in calories. Under CR there was a dynamic change in body mass over 30 days and thereafter it stabilized. The time to reach stability was independent of the level of restriction. At the end of three months whole body dissections revealed differential utilization of the different tissues. Adipose tissue depots were the most significantly utilized tissue, and provided 55.8 to 60.9% of the total released energy. In comparison, reductions in the sizes of structural tissues contributed between 29.8 and 38.7% of the energy. The balance was made up by relatively small changes in the vital organs. The components of the alimentary tract grew slightly under restriction, particularly the stomach, and this was associated with a parallel increase in assimilation efficiency of the food (averaging 1.73%). None of the changes under CR were recapitulated by equivalent levels of PR.