Background: In moderate-to-severe chronic obstructive pulmonary disease (COPD) patients the 6-min walk test (6MWT) is often exhaustive and correlates with the incremental cycle cardiopulmonary exercise test (CPET). Objectives: The aim of this study was to assess the agreement between oxygen uptake (VO<sub>2</sub>) measured during the 6MWT by portable equipment and incremental cycle exercise in COPD patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) I–IV. Methods: A total of 30 patients with COPD GOLD I–IV (14 patients GOLD stage I and II and 16 patients GOLD stage III and IV) underwent a 6MWT and an incremental CPET. Breath-by-breath analysis for VO<sub>2</sub>, carbon dioxide output (VCO<sub>2</sub>), and minute ventilation (VE) were measured during each test. Blood gas analysis and lactate measurements were performed before, during, and after the test. Results: VO<sub>2</sub> in COPD patients GOLD stage I and II was 16.2 ± 4.2 mL/kg/min measured by 6MWT and 20.5 ± 7.0 mL/kg/min measured by CPET as compared to GOLD stage III and IV (11.2 ± 3.7 mL/kg/min measured by 6MWT and 15.5 ± 4.3 mL/kg/min measured by CPET). No significant correlation in VO<sub>2</sub> measurements could be found between both tests in COPD GOLD I and II (r = 0.17), whereas the VO<sub>2</sub> significantly correlated in patients with COPD stage III and IV (r = 0.7). Conclusions: A significant relationship between VO<sub>2</sub> measured by 6MWT and CPET could only be found in patients with more severe COPD but not in milder stages. 6MWT and CPET provide different VO<sub>2</sub> measurements in COPD patients. The two methods cannot be used interchangeably.