Background: Supplemental oxygen is a recommended therapy option in stable hypoxemic COPD patients. Often, supplemental oxygen is provided by continuous flow (CF). However, demand oxygen delivery systems (DODS) that provide an oxygen bolus only during inspiration have gained increasing use as they prolong oxygen cylinder life (beside battery life). However, there is a lack of evidence if different DODS and CF devices are equivalent., Methods: Seventy hypoxemic COPD patients (FEV 1 32 ± 9% predicted, PaO 2 56±7 mmHg) on long-term oxygen therapy were included in this prospective single-blinded, randomized cross-over trial. Following an initial incremental shuttle walk test, patients performed 3 endurance shuttle walk tests (ESWT) at 85% of their maximum walking speed in random order with: (A) CF (ESWT-CF), (B) a DODS based on liquid oxygen (ESWT-DL) and (C) an DODS oxygen concentrator (ESWT-DC). The primary outcome was oxygen saturation (SpO 2 ) at ESWT isotime. Secondary outcomes were total ESWT duration, heart rate (HR) and breathing frequency (BF) at isotime and dyspnea at end-exercise., Results: SpO 2 at ESWT isotime was not clinically different between devices: 90 ± 4% (CF), 89 ± 5% (DL) and 90 ± 5% (DC). However, 20% of the patients showed a ≥4% lower oxygen desaturation while using a DODS device. Secondary outcomes were similar under the three conditions., Conclusion: Oxygen supplementation via DODS (based on liquid oxygen or as a concentrator) yielded comparable physiological effects during standardized walking in stable hypoxemic COPD patients like CF. However, 20% of patients showed a clinically relevant lower oxygen saturation while using a DODS device. Therefore, we suggest individual testing of oxygen saturation of DODS suitability., (Copyright © 2019 Elsevier Ltd. All rights reserved.)