We tested the hypothesis that energy metabolism in the intestinal crypt epithelial cells of piglets changes during the suckling period. The experiment began with 24 piglets from 8 litters (3 piglets per litter). One piglet from each litter was randomly selected and euthanized at 7, 14, or 21 d of age, respectively. Crypt cells were isolated from the mid-jejunum and protein synthesis was analyzed using isobaric tags for relative and absolute quantification. The production of proteins related to glycolysis was mainly decreased from Days 7 to 14 before increasing up to Day 21. Synthesis of proteins involved in fatty acids, amino acids (glutamate and glutamine), and citrate cycle metabolism was generally down-regulated for samples collected on Days 14 and 21 when compared with levels on Day 7. These results indicate that energy metabolism in the intestinal crypt epithelial cells changes during the suckling period. Furthermore, this pattern of metabolism varies among glucose, fatty acids, and amino acids. Therefore, these findings may be useful in efforts to regulate the intestinal development of piglets.