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Ira Katz,1,2 Marine Pichelin,1 Spyridon Montesantos,1 Min-Yeong Kang,3 Bernard Sapoval,3,4 Kaixian Zhu,5 Charles-Philippe Thevenin,5 Robert McCoy,6 Andrew R Martin,7 Georges Caillibotte1 1Medical R&D, Air Liquide Santé International, Centre de Recherche Paris-Saclay, Les Loges-en-Josas, France; 2Department of Mechanical Engineering, Lafayette College, Easton, PA, USA; 3Physique de la Matière Condensée, CNRS, Ecole Polytechnique, Palaiseau, 4Centre de Mathématiques et de leurs Applications, CNRS, UniverSud, Cachan, 5Centre Explor!, Air Liquide Healthcare, Gentilly, France; 6Valley Inspired Products, Inc, Apple Valley, MN, USA; 7Department of Mechanical Engineering, University of Alberta, Edmonton, AB, Canada Abstract: Oxygen treatment based on intermittent-flow devices with pulse delivery modes available from portable oxygen concentrators (POCs) depends on the characteristics of the delivered pulse such as volume, pulse width (the time of the pulse to be delivered), and pulse delay (the time for the pulse to be initiated from the start of inhalation) as well as a patient’s breathing characteristics, disease state, and respiratory morphology. This article presents a physiological-based analysis of the performance, in terms of blood oxygenation, of a commercial POC at different settings using an in silico model of a COPD patient at rest and during exercise. The analysis encompasses experimental measurements of pulse volume, width, and time delay of the POC at three different settings and two breathing rates related to rest and exercise. These experimental data of device performance are inputs to a physiological-based model of oxygen uptake that takes into account the real dynamic nature of gas exchange to illustrate how device- and patient-specific factors can affect patient oxygenation. This type of physiological analysis that considers the true effectiveness of oxygen transfer to the blood, as opposed to delivery to the nose (or mouth), can be instructive in applying therapies and designing new devices. Keywords: efficiency, respiratory physiology, respiratory disease, pulsed delivery