BACKGROUND: Gas exchange measurements for carbon dioxide elimination (V CO 2 ) and oxygen consumption (V O 2 ) have been used to derive resting energy expenditure and guide energy prescription. Volumetric capnography is used in intensive care units and provides V CO 2 measurements that could be used for titrating respiratory and nutritional support. We have recently suggested that measuring V CO 2 may be sufficient to obtain a reasonable estimate of energy expenditure. However, data describing the accuracy of gas exchange measurement devices are limited. METHODS: We used an in vitro simulation model to test the accuracy of gas exchange measurements by 2 devices: the CCM Express indirect calorimeter and the NM3, a volumetric capnography monitor. A Huszczuk gas injection system combined with a high-fidelity lung simulator was used to simulate V O 2 and V CO 2 values in the pediatric and adult range. Bland-Altman analysis was used to examine the agreement between the measured and simulated values across a range of tidal volumes and gas exchange values. Additionally, agreement between the 2 devices was examined. RESULTS: During the adult simulation with the CCM Express, the mean bias (95% CI) for V CO 2 values was ؊12.6% (؊16.4 to ؊8.8%) and ؊17.5% (؊19.9 to ؊15.1%) for V O 2 values. For the pediatric simulation with the CCM Express, mean bias for V O 2 was ؊14.7% (؊16.4 to ؊13.0%) and V CO 2 was ؊10.9% (؊13.5 to ؊8.3%). For the adult and pediatric simulations with the NM3, the bias for V CO 2 was ؊8.2% (؊15.7 to ؊0.7%) and ؊8.3% (؊19.4 to ؊2.8%), respectively. Between the 2 devices, the mean bias was ؊4.4% (؊10.2 to 1.3%) and ؊2.3% (؊11.4 to 6.8%) for the adult and pediatric V CO 2 simulations, respectively. CONCLUSIONS: Currently available portable gas exchange monitors demonstrated acceptable agreement with reference V O 2 and V CO 2 values in an in vitro simulation. The devices demonstrated good agreement with each other.