We examined the hypothesis that acute therapeutic glucocorticoid intake could change the contribution of fat and carbohydrate (CHO) in energy production during exercise. Nine healthy recreationally-trained male subjects twice performed submaximal exercise (60 min at 60 % VO2max) after ingestion of placebo (Pla) or 20 mg of prednisolone (Pred), according to a double blind and randomized protocol. Respiratory exchange was monitored during exercise and blood samples were collected at rest, every 10 min during exercise and after 5, 10, and 20 min of passive recovery. Pred intake significantly increased total energy expenditure during exercise, but CHO oxidation was lower and fat oxidation higher after Pred vs. Pla. ACTH and IL-6 concentrations were significantly decreased with Pred during exercise, whereas no variations were found in GH, insulin, blood glucose, and lactate between the 2 treatments. In conclusion, it appears that acute prednisolone systemic administration does reduce total carbohydrate oxidation during submaximal exercise. Further studies are necessary to clarify the mechanisms involved and to determine whether this modification in the substrate oxidation balance under glucocorticoid administration in recreationally-trained male subjects could result in a competitive advantage in elite athletes.