Isomaltulose (ISO) is a disaccharide that is slowly digested, resulting in a slow availability for absorption. The aim of this study was to compare the blood substrate responses and exogenous carbohydrate (CHO) oxidation rates from orally ingested sucrose (SUC) and ISO during moderate intensity exercise. We hypothesized that the oxidation of ISO is lower compared with SUC, resulting in lower plasma glucose and insulin concentrations and subsequent lower CHO and higher fat oxidation rates. Ten trained men [maximal oxygen uptake (VO(2)max), 64 +/- 1 mL/(kg body mass.min)] cycled on 3 occasions for 150 min at 59 +/- 2% VO(2)max and consumed either water (WAT) or 1 of 2 CHO solutions providing 1.1 g/min of CHO in the form of either SUC or ISO. Peak exogenous CHO oxidation rates were higher (P < 0.05) during the SUC trial (0.92 +/- 0.03 g/min) than during the ISO trial (0.54 +/- 0.05 g/min). Total endogenous CHO oxidation over the final 90 min of exercise was lower (P < 0.05) in the SUC trial (107 +/- 10 g) than in the WAT (137 +/- 7 g) and ISO (127 +/- 9 g) trials. Fat oxidation was higher during the WAT trial than during the SUC and ISO trials. ISO resulted in a lower plasma insulin response at 30 min compared with SUC, whereas the glucose response did not differ between the 2 CHO. Oxidation of ingested ISO was significantly less than that of SUC, most likely due to the lower rate of digestion of ISO. A lower CHO delivery and a small difference in plasma insulin may have resulted in higher endogenous CHO use and higher fat oxidation during the ISO trial than during the SUC trial.