Indirect calorimetry (IC), the measurement of airway CO2 elimination (VCO2), O2 [corrected] uptake (VO2) [corrected], and respiratory exchange ratio (RER = VCO2/VO2), is a noninvasive modality for the assessment of body metabolism. In anesthesia, IC can signal critical events and onset of acute metabolic derangements. We have previously demonstrated the accuracy and precision of a new IC measurement system designed for mechanically ventilated patients, comprised of a new clinical bymixer, fast response humidity and temperature sensor, and a flowmeter. However, measurement of IC during spontaneous breathing is challenging because of unstable tidal volume, frequency, and functional residual capacity (FRC). A new device for IC measurements, designed specifically for spontaneous breathing, was validated against a metabolic lung simulator bench setup. In a second study, the same device was used to conduct preoperative measurements of VCO2 and VO2 in 15 patients. Our measurements showed excellent correlation and agreement with metabolic lung simulator values: The average (+/-SD) percent error for airway VCO2 was -4.7% +/- 3.31%; the average (+/-SD) percent error for airway VO2 was -0.30% +/- 5.25%. Average values of VCO2 and VO2 in the patient study (3.01 +/- 0.56 and 3.44 +/- 0.69 mL x kg(-1) x min(-1), respectively) were in agreement with previously reported values. We have shown that the new, portable bymixer-flow device, using a bymixer and a fast response humidity sensor, provided accurate and convenient bedside measurement of VCO2 and VO2. We believe that it can contribute in the future to preoperative assessment and baseline reference value for perioperative management.