This study reports on the preparation and characterization of porous clay heterostructures (PCH) as a high-surface-area support for CuO-CeO2 based catalysts for the preferential oxidation of CO in excess of H-2 ( CO-PROX). After pillaring the montmorillonite clay with silica (Si-PCH) and silica-zirconia (SiZr-PCH), the Cu-Ce active phase was loaded by incipient wet impregnation setting the cerium amount constant (20 wt%) and investigating three different copper loadings (3, 6 and 12 wt%). The use of pillars of silica or silica-zirconia inserted in the interlayer space of a natural clay provides a high surface area support that can favor the dispersion of both CuO and CeO2 active phases, leading to the formation of a high amount of copper-ceria interfacial sites, responsible for a very high catalytic activity in the CO-PROX reaction. The results obtained from characterization of the materials by XRD, N-2 physisorption, H-2-TPR, XPS and CO2-TPD suggest that this synthesis method gives rise to catalysts with copper species highly active and selective for the CO-PROX reaction. The catalysts exhibit high CO conversion values and the sample with 6 wt% of copper on Si-PCH displays very good performances, comparable to those based on precious metal catalysts, even at low temperatures. The system reducibility was found modified by the incorporation of zirconium in the support, with a slight decrement of the CO conversion value, compared to the same material without Zr. The influence of the presence of CO2 and H2O in the gas feed was also studied in order to simulate the real operating conditions of a PEMFC feed stream. Correlations between catalytic performances and physicochemical properties of the materials have been made. (C) 2015 Elsevier B.V. All rights reserved.