Background and aim: Glycemic index (GI) and Glycemic Load (GL) are parameters of carbohydrate bioavailability able to influence risk of chronic diseases. GL can be lowered either by reducing carbohydrate intake or by reducing the GI of the carbohydrate moiety of a mixed meal. These two approaches might have a different impact on Dietary-Induced Thermogenesis (DIT) and preferential substrate oxidation in the postprandial period, which are variables known to be involved in the regulation of body weight and body composition. This dietary, crossover intervention trial was designed to evaluate the effect on DIT and Respiratory Quotient (RQ) of three isocaloric breakfasts different in GI and/or GL (high GI and high GL [HGIeHGL] vs. low GI and low GL [LGIeLGL]; vs. high GI and low GL [HGIeLGL]) followed by a standard meal. Methods and results: RQ and DIT were measured in 16 lean young males by indirect calorimetry for 8 h. DIT resulted significantly higher after the LGIeLGL compared to the HGIeHGL breakfast (p