Previous selection experiments using residual feed intake (RFI) to select pigs with a high feed efficiency have reported that a low RFI was associated with a reduced body fat content and a greater muscle glycogen content. In the current study, growing Large White female piglets from 2 lines divergently selected for RFI were used to determine the changes in energy and protein metabolisms in key tissues and their cross talks in response to selection. Pigs of low RFI (RFI(-); n = 26) or high RFI (RFI(+); n = 36) selection lines were offered free access to feed during postweaning and growing periods. Pigs of each line were then slaughtered at 19 kg (n = 8 per line) or 115 kg BW (n = 14 to 18 per line). A third group of pigs of the RFI(+) line was offered feed at the same level per metabolic BW (BW0.60) as RFI- pigs (group RFI+R, n = 14). Regardless of the growth period considered, G:F was less in RFI(+) pigs than in RFI(-) pigs. At 19 kg BW, RFI(+) and RFI(-) pigs had a similar body composition and tissue lipid content. The fractional rate of protein synthesis and proteasome activity were decreased (P < 0.090) in the livers of RFI(+) pigs compared with RFI(-) pigs whereas activities of energy catabolic enzymes did not differ in the liver and LM samples. Plasma insulin was conversely greater (P = 0.049) in RFI(+) pigs at this stage. At 115 kg BW, enzyme activities of protein catabolism in the liver and in the LM did not differ (P > 0.10) between RFI(+) pigs and RFI(-) pigs. Both lactate dehydrogenase activity participating in glucose metabolism and hydroxylacylCoA dehydrogenase activity involved in fatty acid oxidation were greater (P < 0.05) in the liver and LM of RFI(+) pigs compared with RFI(-) pigs. In the liver, contrary to the LM, those differences in enzyme activities were directly associated with selection on RFI regardless of ADFI. Increased backfat depth and content and greater lipid content and adipocyte hypertrophy (P < 0.05) in subcutaneous adipose tissue were reported in RFI(+) pigs compared with RFI(-) pigs at 115 kg BW without marked changes in key lipogenic enzyme activities; these changes were directly associated with ADFI. In conclusion, the present study shows an increase of catabolic pathway activities in the liver and muscle of RFI(+) pigs at market weight that is likely to generate more ATP compared with RFI(-) pigs.