Background & aims: Indirect calorimetry is recommended to measure energy expenditure (EE) in critically ill, mechanically ventilated patients. The most validated system, the Deltatrac® (Datex-Ohmeda, Helsinki, Finland) is no longer in production. We tested the agreement of a new breath-by-breath metabolic monitor E-sCOVX® (GE healthcare, Helsinki, Finland), with the Deltatrac. We also compared the performance of the E-sCOVX to commonly used predictive equations. Methods: We included mechanically ventilated patients eligible to undergo indirect calorimetry. After a stabilization period, EE was measured simultaneously with the Deltatrac and the E-sCOVX for 2 h. Agreement and precision of the E-sCOVX was tested by determining bias, limits of agreement and agreement rates compared to the Deltatrac. Performance of the E-sCOVX was also compared to four predictive equations: the 25 kcal/kg, Penn State University 2003b, Faisy, and Harris–Benedict equation. Results: We performed 29 measurements in 16 patients. Mean EE-Deltatrac was 1942 ± 274 kcal/day, and mean EE-E-sCOVX was 2177 ± 319 kcal/day (p < 0.001). E-sCOVX overestimated EE with a bias of 235 ± 149 kcal/day, being 12.1% of EE-Deltatrac. Limits of agreement were −63 to +532 kcal/day. The 10% and 15% agreement rates of EE-E-sCOVX compared to the Deltatrac were 34% and 72% respectively. The bias of E-sCOVX was lower than the bias of the 25 kcal/kg-equation, but higher than bias of the other equations. Agreement rates for E-sCOVX were similar to the equations. The Faisy-equation had the highest 15% agreement rate. Conclusion: The E-sCOVX metabolic monitor is not accurate in estimating EE in critically ill mechanically ventilated patients when compared to the Deltatrac, the present reference method. The E-sCOVX overestimates EE with a bias and precision that are clinically unacceptable.