To determine the effects of creatine supplementation on cardiorespiratory responses during a graded exercise test (GXT) 36 trained adults (20 male, 16 female; 21–27 years old) performed two maximal GXTs on a cycle ergometer. The first GXT was done in a non-supplemented condition, and the second GXT was done following 7 days of ingesting either 5 g creatine monohydrate, encased in gelatin capsules, four times daily (CS, 13 male, 6 female), or the same number of glucose capsules (PL, 7 male, 10 female). CS significantly (P < 0.05) improved total test time [pre-CS=1217 (240) s, mean (std. dev.) versus post-CS=1289 (215) s], while PL administration had no effect (P > 0.05) on total test time [pre-PL=1037 (181) s versus post-PL=1047 (172) s]. In addition, both oxygen consumption (V˙ _O2) and heart rate at the end of each of the first five GXT stages were significantly lower after CS, but were unchanged after PL. Moreover, the ventilatory threshold occurred at a significantly greater V˙ _O2 for CS [pre-CS=2.2 (0.4) l � min⁻¹ or 66% of peak V˙ _O2 versus post-CS=2.6 (0.5) l � min⁻¹ or 78% of peak V˙ _O2; pre-PL=2.6 (0.9) l � min⁻¹ or 70% peak V˙ _O2 versus post-PL=2.6 (1.1) l � min⁻¹ or 68% of peak V˙ _O2]. Neither CS nor PL had an effect on peak V˙ _O2 [pre-CS=3.4 (0.7) l � min⁻¹ versus post-CS=3.3 (0.7) l � min⁻¹; pre-PL=3.7 (1.1) l � min⁻¹ versus post-PL=3.7 (1.1) l � min⁻¹]. Apparently, CS can alter the contributions of the different metabolic systems during the initial stages of a GXT. Thus, the body is able to perform the sub-maximal workloads at a lower oxygen cost with a concomitant reduction in the work performed by the cardiovascular system.