Co3O4 is one of the most promising catalysts for CO catalytic combustion. Nevertheless, the roles of Co2+ and Co3+ in the catalytic combustion process are still incompletely explored. Existing studies mostly focused on the role of Co3+, but the role of Co2+, and the interactions between the Co3+ and Co2+ are ignored. The catalytic activity of different Co sites is always affected by the electronic structure and the adsorption ability towards gas molecule, but clarifying the role of a single site is difficult due to the coexistence of Co2+ and Co3+. Herein, for exploring the role of single Co2+ or Co3+ site and their interaction, the Co2+ and Co3+ sites were replaced by Zn2+ and Al3+, respectively, which are more inert in CO catalytic combustion. According to catalytic activity measurement, the catalytic performance follows the order that: Co3O4(T90 = 153 °C) > ZnCo2O4(T90 = 189 °C) > CoAl2O4(T90 = 292 ℃). The experimental and calculation results showed that both Co2+ and Co3+ could act as active sites for CO catalytic combustion. CO and O2 are more prone to be absorbed over Co3+ and Co2+ sites, respectively. Co2+ and Co3+ make adsorbed oxygen and surface lattice oxygen highly reactive, respectively. The interaction between Co3+ and Co2+ is also important. The coexistence of Co2+ and Co3+ could increase the ratio of lattice oxygen and avoid the competitive adsorption between CO and O2, thereby Co3O4 showed the excellent catalytic performance.