Display omitted ► CO oxidation using the metal–organic framework HKUST-1 and Ce/HKUST-1. ► Slow segregation of active 5–15nm CuO particles upon MOF collapse. ► Synthesis of the highly active CuO–Ce2O nanoparticle catalyst. ► Effective route to immobilize nanoparticles in a monolith reactor. The oxidation of carbon monoxide using the metal organic framework (MOF) HKUST-1 is studied. Catalytic results and characterizations by XRD, TEM, H2-TPR, SEM and LRS show that HKUST-1 itself is not effective in CO oxidation, but is activated in the reaction atmosphere segregating active 5–15nm CuO particles upon the collapse of the MOF structure. Furthermore, the microporous structure of HKUST-1 is effective to disperse Ce precursors which, upon activation, allow the synthesis of a mixture of CuO and CeO2 nanoparticles in intimate contact. These nanoparticles present a very high activity in CO oxidation. It is shown that this synthesis route employing HKUST-1 as a matrix is useful to immobilize CuO–Ce2O nanoparticles in a monolithic reactor, while keeping a high catalytic activity.