This study investigated the influence of the addition of copper on the catalytic performance of the NiO-CeO2 system for preferential CO oxidation reaction (CO-PROX) in hydrogen excess. A systematic structural characterization was performed employing various techniques (XRD, H-2-TPR, Raman spectroscopy, HRTEM and XPS) in order to understand the structure-activity relationship. XRD, Raman and HRTEM analysis showed that part of Ni is introduced into the CeO2 structure forming a Ce1-xNixO2 solid solution and maintaining the fluorite structure, while Cu species added a posteriori are dispersed on the ceria surface. The catalytic performance of NiO-CeO2 system was significantly improved by addition of copper. This enhance in CO activity was attributed to synergetic interaction between dispersed copper species and surface oxygen vacancies of ceria support. Conversely, the effect of the presence of copper was not beneficial to the stability. XRD patterns of the catalyst post reaction indicate that metallic Cu and Ni were formed during the course of CO-PROX reaction, while Raman analysis demonstrates the both catalysts presented high resistance to carbon deposition. These results suggest that the decline in CO conversion and CO2 selectivity observed during the stability tests was caused by partial reduction of nickel and copper oxides sites (favored at higher temperatures). In addition, the influence of H2O and CO2 affected severely the reaction rate, however it is totally reversible. (C) 2015 Elsevier B.V. All rights reserved.