We explore the mechanism of CO oxidation on Cun and CunO (n = 6,7) clusters including both Eley–Rideal (ER) and Langmuir–Hinshelwood (LH) based on spin–polarized density functional theory calculations.We find that 1) ER mechanism prevails over LH in all the systems except for Cu7O; 2) the incoming molecular O2 is more likely to directly participate in the formation of CO2 than the intrinsic O in the oxide clusters; 3) pure Cun clusters are more active to the reactions with respect to the corresponding oxide clusters.Our calculations further reveal that the reaction will be much easier when the geometric and electronic structures of the transition state (TS) are closer to those of the reactants (similar to the concept of “early transition state” in organic reactions); conversely,the reaction rate will be lower if they resemble those of the products more (late TS).