AbstractThis study aimed to compare the Cosmed K5 portable indirect calorimeter, using the mixing chamber mode and face mask, with a stationary metabolic cart when measuring the resting metabolic rate (RMR) and to derive fitting equations if discrepancies are observed. Forty‐three adults (18–84 years) were assessed for their RMR for two 30‐min consecutive and counterbalanced periods using a Cosmed K5 and an Oxycon Pro. Differences among devices were tested using paired sample Student's t‐tests, and correlation and agreement were assessed using Pearson's correlation coefficients, intraclass correlation coefficient and Bland–Altman plots. Forward stepwise multiple linear regression models were performed to develop fitting equations for estimating differences among devices when assessing oxygen uptake (VO₂^diff, mL·min⁻¹) and carbon dioxide production (VCO₂^diff, mL·min⁻¹). Furthermore, the Oxycon Pro was tested before being confirmed as a reference device. Significant differences between devices were found in most metabolic and ventilatory parameters, including the primary outcomes of VO₂ and VCO₂. These differences showed an overestimation of the Cosmed K5 in all metabolic outcomes, except for Fat, when compared to the Oxycon Pro. When derived fitting equations were applied (VO₂^diff − 139.210 + 0.786 [weight, kg] + 1.761 [height, cm] – 0.941 [Cosmed K5 VO₂, mL·min⁻¹]; VCO₂^diff − 86.569 + 0.548 [weight, kg] + 0.915 [height, cm] – 0.728 [Cosmed K5 VCO₂, mL·min⁻¹]), differences were minimized, and agreement was maximized. This study provides fitting equations which allow the use of the Cosmed K5 for reasonably optimal RMR determinations.