Cu and Ni were supported on ZrO2 by co-impregnation and sequential impregnation methods, and tested in the oxidative steam reforming of methanol (OSRM) reaction for H-2 production as a function of temperature. Surface area of the catalysts showed differences as a function of the order in which the metals were added to zirconia. Among them, the Cu/ZrO2 catalyst had the lowest surface area. XRD patterns of the bimetallic catalysts did not show diffraction peaks of the Cu, Ni or bimetallic Cu Ni alloys. In addition, TPR profiles of the bimetallic catalysts had the lowest reduction temperature compared with the monometallic samples. The reactivity of the catalysts in the range of 250-350 degrees C showed that the bimetallic samples prepared by successive impregnation had highest catalytic activity among all the catalysts studied. These results were also confirmed by theoretical calculations. The reactivity of the monometallic and bimetallic structures obtained by molecular simulation followed the next order: NishellCucore/ZrO2 congruent to CushellNicore/ZrO2 > Ni/Cu/ZrO2 > Cu/Ni/ZrO2 > Cu-Ni/ZrO2 > Cu/ZrO2 > Ni/ZrO2. These findings agree with the experimental results, indicating that the bimetallic catalysts prepared by successive impregnation show a higher reactivity than the Cu Ni system obtained by co-impregnation. In addition, the selectivity for H-2 production was higher on these catalysts. This result could be associated also to the presence of the bimetallic Cu-Ni and core-shell Ni/Cu nanoparticles on the catalysts, as was evidenced by TEM-EDX analysis, suggesting that the OSRM reaction may be a structure-sensitive reaction. Copyright (C) 2012, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.