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There are several methods available to assess energy expenditure, all associated with inherent pros and cons that must be adequately considered for use in specific environments and populations. A requirement of all methods is that they must be valid and reliable in their capability to accurately measure oxygen consumption (VO₂) and carbon dioxide production (VCO₂). The purpose of this study was to evaluate the reliability and validity of the mobile CO₂/O₂ Breath and Respiration Analyzer (COBRA) relative to a criterion system (Parvomedics TrueOne 2400^®, PARVO) with additional measurements to compare the COBRA to a portable system (Vyaire Medical, Oxycon Mobile^®, OXY). Fourteen volunteers with a mean of 24 years old, body weight of 76 kg, and a VO_2peak of 3.8 L∙min⁻¹ performed four repeated trials of progressive exercises. Simultaneous steady-state measurements of VO₂, VCO₂, and minute ventilation (V_E) by the COBRA/PARVO and OXY systems were conducted at rest, while walking (23–36% VO_2peak), jogging (49–67% VO_2peak), and running (60–76% VO_2peak). Data collection was randomized by the order of system tested (COBRA/PARVO and OXY) and was standardized to maintain work intensity (rest to run) progression across study trials and days (two trials/day over two days). Systematic bias was examined to assess the accuracy of the COBRA to PARVO and OXY to PARVO across work intensities. Intra- and inter-unit variability were assessed with interclass correlation coefficients (ICC) and a 95% limit of agreement intervals. The COBRA and PARVO produced similar measures for VO₂ (Bias ± SD, 0.01 ± 0.13 L·min⁻¹; 95% LoA, (−0.24, 0.27 L·min⁻¹); R² = 0.982), VCO₂ (0.06 ± 0.13 L·min⁻¹; (−0.19, 0.31 L·min⁻¹); R² = 0.982), V_E (2.07 ± 2.76 L·min⁻¹; (−3.35, 7.49 L·min⁻¹); R² = 0.991) across work intensities. There was a linear bias across both the COBRA and OXY with increased work intensity. The coefficient of variation for the COBRA ranged from 7 to 9% across measures for VO₂, VCO₂, and V_E. COBRA was reliable across measurements for VO₂ (ICC = 0.825; 0.951), VCO₂ (ICC = 0.785; 0.876), and V_E (ICC = 0.857; 0.945) for intra-unit reliability, respectively. The COBRA is an accurate and reliable mobile system for measuring gas exchange at rest and across a range of work intensities.