Background: In recent years, lactose-free infant formulas have been increasingly used. Digestible maltodextrins are commonly used as a substitute for lactose in these formulas, but the effects on energy metabolism are unknown. Objective: We aimed to evaluate the differences in energy metabolism and substrate oxidation in piglets fed milk replacers containing lactose compared with maltodextrin as the only source of carbohydrates. Methods: Piglets (Tempo × Topigs 20) from 8 litters were fed milk replacers containing lactose or maltodextrin (28% w/w, milk powder basis) from 1 to 9 wk of age (n = 4 litters/milk replacer). At 5 wk of age, 4 females and 4 entire males (mean ± SEM bodyweight, 10 ± 0.3 kg) were selected per litter, and housed in 16 groups of 4 littermates, with 2 females and 2 males per pen (n = 8 groups/milk replacer). Between 7 and 9 wk of age, groups were housed for 72 h in climate respiration chambers, and fed their experimental milk replacer in 2 meals per day, at 08:30 and 16:30. Heat production data were calculated from the continuous measurement of gaseous exchanges and analyzed using general linear models in SAS. Results: Resting metabolic rate was 6% less in maltodextrin- than in lactose-fed piglets, notably before the morning meal. The postprandial respiratory quotient was 13% greater inmaltodextrin- than in lactose-fed piglets after bothmeals. Net rates of carbohydrate oxidation were on average 5% greater in maltodextrin- than in lactose-fed piglets, particularly after the afternoon meal, whereas net rates of fat oxidation were 9% less in maltodextrin- than in lactose-fed piglets, particularly after the morning meal. Conclusions: Compared with lactose, maltodextrin in milk replacers reduced resting metabolic rate in the fasting state, and induced a shift in postprandial substrate oxidation profiles in pigs. Further research is warranted to evaluate the consequences of these metabolic changes for body composition.