We have studied the catalytic carbon monoxide (CO) oxidation (CO+0.5O 2 → CO 2) reaction using a powder catalyst composed of both copper (5wt% loading) and titania (CuO x-TiO 2). Our study was focused on revealing the role of Cu, and the interaction between Cu and TiO 2 , by systematic comparison between two nanocatalysts, CuO x-TiO 2 and pure CuO x. We interrogated these catal ysts under in situ conditions using X-ray Diffraction (XRD), X-ray Absorption Fine Structure (XAFS) and Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS) to probe the structure and electronic properties of the catalyst at all stages of the reaction and simultaneously probe the surface states or intermediates of this reaction. With the aid of several ex situ characterization techniques including Transmission Electron Microscopy (TEM), the local catalyst morphology and structure was also studied. Our results show that a CuO x-TiO 2 system is more active than bulk CuO x for the CO oxidation reaction due to its lower onset temperature and better stability at higher temperatures. Our results also suggests that a surface Cu + species observed in the CuO x-TiO 2 interface are likely to be a key player in the CO oxidation mechanism, while implicating that the stabilization of this species is probably associated with the oxide-oxide interface. Both in situ DRIFTS and XAFS measurements reveal that there is likely to be a Cu(Ti)-O mixed oxide at this interface. We discuss the nature of this Cu(Ti)-O interface and interpret its role on the CO oxidation reaction.