A catalyst of copper oxide supported on nanoStructured ceria has been examined with the aim of exploring deactivating effects produced by CO2 or H2O presence on its activity for preferential oxidation of CO in a H-2-rich stream. For this purpose, the catalyst is explored by means of operando-DRIFTS experiments. The results allow determining most relevant deactivating effects induced by CO2 and H2O. These are mainly related to modifications of interfacial sites upon formation of specific carbonates and a blocking effect induced by the presence of adsorbed molecular water, respectively, which limit redox/catalytic activity of the interfacial zone of the catalyst active for CO oxidation. Such modifications are directly evidenced by the difficulties of ceria to promote the generation of partially reduced states at interfacial sites of the dispersed copper oxide particles or to propagate the reduction over such particles, which affects to the hydrogen oxidation activity of the catalyst, leading on the whole to a general decrease of the CO-PROX performance of the system. (C) 2009 Elsevier Inc. All rights reserved.