<p>Copper doped on cobalt oxide-based catalysts prepared by hydrothermal and reflux methods were investigated for preferential oxidation of carbon monoxide (CO(PrOx) in hydrogen rich stream. The FTIR spectra of as-prepared catalysts showed the presence of Co³⁺–O²⁻ and Co²⁺–O²⁻ stretching vibrations arising from Co₃O₄ spinel crystal structure, as confirmed by the XRD, TEM, and H₂-TPR data. The reflux prepared 5 wt% CuOx/Co₃O₄ catalyst demonstrated a notable CO conversion of 91% at 80&#xa0;°C, compared to its hydrothermal counterpart. The activity is correlated with strong Cu–Co interactions within the spinel matrix and the unique catalyst morphology. These favoured the formation of high surface oxygen vacancies and small crystallite size (~ 5.5&#xa0;nm), contributing to large pore structure and higher BET surface area of 64.9 m²/g. The surface oxidation states of Cu and Co were revealed to consists of Cu⁺, Cu²⁺, Co²⁺ and Co³⁺ by the XPS spectra, which drove Cu⁺+ Co³⁺↔Cu²⁺+ Co²⁺ redox synergy. A decrease in content of active species (Cu⁺ and Co³⁺) with time on stream was observed during CO(PrOx). The as prepared 5 wt% CuO_x/Co₃O₄(Ref) catalyst showed good stability under dry and CO₂ environments, and its activity deactivate in moisture environment. This work offers a novel strategy for preparation of active CO(PrOx) catalysts with the aim to promote adoption of proton exchange membrane fuel cell (PEMFC) technology.</p>