We studied the combined effects of energy and protein contents on food selection by the white-footed mouse, Peromyscus leucopus. Our objective was to determine how variation in levels of a food component affected the overall attractiveness of a food to the mice and whether trade-offs are made in selecting dietary protein compared with energy. We conducted food-selection tests in the laboratory and field using foods containing different combinations of energy and protein levels. In the laboratory, P. leucopus were offered a choice between a high-energy and a low-energy food with the protein level held constant and between a high-protein and a low-protein food with the energy level held constant. The field study was set up to offer an encounter with all four combinations of energy and protein simultaneously. We also tested for preferred levels of protein using pairwise food-selection tests in the laboratory. In the laboratory and field tests, P. leucopus selected high-energy foods that were low in protein, but avoided all foods with a high protein content. When given pairwise choices among foods containing 5, 15, 25, or 35% protein, P. leucopus consistently preferred the food with 15% protein. Peromyscus leucopus quickly detected differences in protein and energy levels in foods, selecting specific foods according to metabolic profitability and nutrient needs.