Critically ill patients are subjected to routine clinical activities that increase oxygen demand. This results in increased heart rate, blood pressure, minute ventilation, and oxygen delivery in patients with often already compromised cardiopulmonary systems. This study examines whether the benzodiazepine, midazolam, could attenuate the increase in metabolism, respiration, and circulation seen during chest physical therapy. Two groups of mechanically ventilated postoperative patients were studied. One group (n = 15) received, in random order, 0.015 mg/kg of midazolam and placebo prior to two consecutive chest physical therapy sessions, while the other (n = 13) received 0.030 mg/kg and placebo. Both doses of midazolam significantly attenuated the increases in oxygen consumption, heart rate, and systemic blood pressure observed during placebo administration. The cardiac output increase was also attenuated. Although midazolam reduced minute ventilation and respiratory rate, no excess CO2 retention occurred when the drug was administered likely as the result of reduced CO2 production. The administration of midazolam (0.015 mg/kg and 0.030 mg/kg) prior to chest physical therapy reduces metabolic, hemodynamic, and ventilatory responses to chest physical therapy.