This study aimed to examine the validity, reliability and minimum detectable change (MDC) of the Cosmed K5 in breath by breath (BxB) mode, against VacuMed metabolic simulator. Intra and inter-units reliability was also assessed. Fourteen metabolic rates (from 0.9 to 4 L.min-1) were reproduced by a VacuMed system and pulmonary ventilation (VE), oxygen consumption (VO₂) and carbon dioxide production (VCO₂) were measured by two different K5 units. Validity was assessed by ordinary least products (OLP) regression analysis, Bland-Altman plots, intraclass correlation coefficients (ICC), mean percentage differences, technical errors (TE) and MDC for VE, VO₂, and VCO₂. Intra- and inter-K5 reliability was evaluated by absolute percentage differences between measurements (MAPE), ICCs, TE, and MDC. Validity analysis from OLP regression data and Bland- Altman plots indicated high agreement between K5 and simulator. ICC values were excellent for all variables (>0.99). Mean percentage differences in VE (-0.50%, p = 0.11), VO₂ (-0.04%, p = 0.80), and VCO₂ (-1.03%, p = 0.09) showed no significant bias. The technical error (TE) ranged from 0.73% to 1.34% (VE and VCO₂ respectively). MDC were lower than 4% (VE = 2.0%, VO₂ = 3.8%, VCO₂ = 3.7%). The intra and inter K5 reliability assessment reveled excellent ICCs (>0.99), MAPE <2% (no significant differences between trials), TE < or around 1%, MDC <or around 3%. K5 in BxB mode is a valid and reliable system for metabolic measurements. This is the first study assessing the MDC accounting only for technical variability reporting intra- and inter-units MDCs <3.3%.