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 VO2peak of 3.8 L∙min-1 performed four repeated trials of progressive exercises. Simultaneous steady-state measurements of VO2, VCO2, and minute ventilation (VE) by the COBRA/PARVO and OXY systems were conducted at rest, while walking (23-36% VO2peak), jogging (49-67% VO2peak), and running (60-76% VO2peak). 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), VE (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 VE. COBRA was reliable across measurements for VO2 (ICC = 0.825; 0.951), VCO2 (ICC = 0.785; 0.876), and VE (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.