A pilot investigation regarding the CO oxidation mechanism at the Co3O4(110) surface is performed by means of first-principles calculations based on density functional theory. Preferred adsorption of CO is found to occur at a surface Co3+ site. A possible mechanism for CO2(g) formation of the Mars-van Krevelen type is also looked into via the monitoring of two inequivalent oxygen abstraction routes. Experimental observations regarding partial surface deactivation are discussed based on surface intermediates. The oxidative property of the CO3O4 substrate, i.e., Co3+ + e- --> Co2+, is found to be crucial for the O abstraction step. This implies that CoAl2O4 is inactive in CO oxidation, in agreement with experiment.