We measured oxygen consumption (VO2) during spontaneous breathing with continuous positive airway pressure (CPAP), assist control ventilation (AC), and control ventilation during muscle relaxation (AC-MR) in eight patients undergoing resuscitation from cardiopulmonary failure. VO2 decreased in all eight patients between CPAP and AC-MR; mean VO2 (255 +/- 92 ml/min) on CPAP exceeded that on AC-MR (209 +/- 79 ml/min) (p < 0.005). Compared with CPAP, AC without MR reduced VO2 in five of eight patients and mean VO2 (227 +/- 59 ml/min) tended to decrease (p = 0.14); clinical examination did not distinguish patients requiring MR to reduce VO2 further. If VO2 on CPAP approximates VO2 during spontaneous breathing, the difference between CPAP and AC-MR (VO2resp) represents the decrement of VO2 that can be obtained during muscle rest. Both VO2resp and the mechanical work performed by the ventilator on the respiratory system were increased to about five times the efficiencies reported for normal patients, but VO2resp did not correlate with the mechanical work because of a wide range of respiratory muscle efficiencies. These efficiencies are less than those reported in normal patients, which may reflect the effect of sepsis, acidemia, hypoxia, or other conditions in these patients. We conclude that mechanical ventilation with muscle relaxation reduces VO2 by more than 20%; beyond stabilizing pulmonary gas exchange, these interventions preserve limited O2 delivery (QO2) for other vital organs.