Abstract: Chemical looping reforming of methane to syngas (CO and H₂) is one of the most promising routes for methane utilization, where the further reaction of CO on oxygen carrier surfaces is a primary determinant of CO selectivity. In this work, the effects of oxygen vacancy (V_O) on CO desorption, CO oxidation, and CO dissociation are systematically studied by using density functional theory calculations. Our calculated results reveal that increasing V_O concentration can weaken CO desorption at Fe sites due to the enhanced localization of electrons in the Fe atoms. Also, the increase in V_O concentration from 1/12 ML to 1/6 ML leads to a dramatic increase of activation energy in the CO oxidation from 0.64 eV to 1.10 eV. Moreover, the increase in V_O concentration is conducive to CO dissociation, but the dissociation is still almost impossible due to the high reaction energies (large than 3.00 eV). Considering these three reaction paths, CO desorption can proceed spontaneously at reaction temperatures above 900 K. Increasing V_O concentration can improve the selectivity of syngas production due to the less favorable CO oxidation compared with CO desorption at high V_O concentrations (1/6 ML). This work reveals the microscopic mechanism that CO selectivity rises in the CLRM as the degree of Fe₂O₃ reduction increases.