Measurement of gas exchange using portable metabolic carts to indirectly determine energy expenditure (EE) has been a recent advance in the nutritional management of mechanically ventilated, critically ill patients. Although administration of large doses of morphine has been shown to significantly decrease EE, the influence on EE of morphine given in routine amounts to critically ill patients has not been studied previously. We examined the effect of morphine administration (given as bolus IV injections of 0.10 mg/kg every two hours and continuous IV infusion at 0.05 mg/kg/hr) on EE during rest and various ICU activities in seven mechanically ventilated patients. Morphine administration resulted in a significant reduction in resting EE and total EE of 6.0 and 8.6 percent, respectively. However, EE associated with activities (ie, chest x-ray examination and chest physiotherapy) were not significantly affected by morphine administration. Both bolus and continuous IV morphine infusion had similar effects on EE. Administration of routine doses of morphine significantly decreases total EE in critically ill patients. This should be considered an important factor influencing measurements of EE.