Ventilation in the prone position improves the prognosis of patients with severe acute respiratory distress syndrome (ARDS). Contraindications to ventilation in this position include unstable systemic circulation. Only a few reports exist on the effects of prone ventilation in respiratory failure on systemic circulation. This animal study compared systemic hemodynamic changes between supine and prone positions in anesthetized rabbits under acute systemic hypoxia (breathing 15% O2). Cardiac output and the systemic O2 extraction ratio increased under the hypoxia, but only in the supine group. Besides, the rate pressure product was higher in the prone group than in the supine group. This study showed that prone ventilation increases myocardial O2 consumption and suppresses compensatory mechanisms to maintain aerobic metabolism during systemic hypoxia. First of all, it will be necessary to examine the effect of prone ventilation on the O2 supply-demand balance in the ARDS model.