Properties of co-precipitated CuO/CeO₂ catalysts with nominal content of 1–3 wt.% copper were investigated by EDS, XRD, BET, STEM, EDS map, H₂-TPR, in situ DRIFTS and in situ XANES. By comparing results of DRIFTS, XANES and catalytic performance in the CO-PROX reaction, it was evidenced a relationship between the catalytic behavior and the copper oxidation state of the materials. In situ DRIFTS and XANES analyses shed light on the oxidation state of active copper species involved in the CO-PROX reaction between 120 °C and 200 °C. The investigated catalysts present a balance between Cu° and Cu⁺ species under PROX conditions and the Cu⁺ is the main species liable to adsorb CO. Furthermore, our studies indicated that the PROX reaction on CuO/CeO₂ is impacted by the nature of Cu species, which in turn may vary with reaction temperature, depending on the Cu content. From these results, we propose a new mechanism of PROX reaction on CuCe catalysts, including Cu°/Cu⁺ and Ce³⁺/Ce⁴⁺ redox pairs and direct CO oxidation on Cu°.