The impact of slow digestible sources of dietary carbohydrate in reducing the risk of developing obesity and related metabolic disorders is unclear. The aim of the present study was to compare the postprandial metabolic response to the ingestion of sucrose v. isomaltulose. We hypothesised that the reduced digestion and absorption rate of isomaltulose would result in lower glycaemic and insulinaemic responses when compared with the ingestion of sucrose, leading to greater postprandial fat oxidation rates. In a randomised, single-blind, cross-over study, ten overweight subjects ingested two different carbohydrate drinks (sucrose and isomaltulose, 75 g carbohydrate equivalents) following an overnight fast (08.40 hours) and with a standardised meal (12.30 hours, 25 % of total energy content was provided as either a sucrose or isomaltulose drink). Blood samples were taken before ingestion and every 30 min thereafter for a period of 3 h, substrate use was assessed by indirect calorimetry and breath samples were collected. Ingestion of carbohydrates with a mixed meal resulted in a lower peak glucose and insulin response and a lower change in area under the curve (DeltaAUC) following isomaltulose when compared with sucrose. Together with the lower glucose and insulin responses, postprandial fat oxidation rates were higher (14 %) with isomaltulose when compared with sucrose when ingested with a mixed meal (P = 0.02). The attenuated rise in glucose and insulin concentrations following isomaltulose results in reduced inhibition of postprandial fat oxidation. The metabolic response to isomaltulose co-ingestion suggests that this may represent an effective nutritional strategy to counteract overweight-induced metabolic disturbances.