In the preferential oxidation of CO in hydrogen mixtures (PROX), CO and H-2 oxidation occur in parallel on the surface in a porous catalyst. The diffusion of the reactants into the pore structure of the catalyst can affect the catalyst performance significantly, and its effect can be accounted for in terms of the effectiveness factor. Conventional methods for estimating the effectiveness factor are not directly applicable because they have been developed for a single reaction in a catalyst particle. A novel method for a simultaneous estimation of the effectiveness factors of the two reactions was developed in this study. This method is based on the PROX kinetics over a CuO-CeO2 catalyst and is applicable to the cases where the CO oxidation can be approximated by a first-order reaction and both oxidations are zero-order reactions with respect to the O-2 partial pressure. With the method, the performance of an isothermal PROX reactor was simulated to determine the effects of the feed flow rate, feed composition, reactor temperature and catalyst size on the CO clean-up. Copyright (c) 2013, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.