The present study was designed as a randomized, double-blind placebo-controlled study to determine the effect of two weeks of growth hormone administration (GH-adm.) on energy expenditure (EE) and substrate oxidation in healthy humans. Sixteen young healthy men were divided into two groups. The study consisted of two 24-h measurements (indirect calorimetry), separated by two weeks of either placebo (Plc)- or GH-injections (6 IU day^-1). At baseline no significant differences were observed between the two groups in any of the measured anthropometric, hormonal or metabolic parameters, neither did the parameters change over time in the Plc- group. GH-adm. resulted in a 4.4 % increase in 24-h EE (P < 0.05) and an increase in fat oxidation by 29 % (P < 0.05). However, a decrease in the respiratory quotient was only observed in the post-absorptive phase after an overnight fast (0.84 ± 0.1 to 0.79 ± 0.1, P < 0.05). Furthermore, lean body mass (LBM) was increased by GH-adm. only (62.8 ± 2.5 kg (baseline) vs. 64.7 ± 2.4 kg (after), P < 0.001). In conclusion, GH-adm. increases 24-h EE, which may be partly explained by increased LBM. Furthermore, GH-adm. stimulates fat combustion especially in the post-absorptive state.