The size and configuration of small Pd ensembles (monomers, dimers, trimers, and tetramers) is of great importance not only for the fundamental understanding of single-site catalysis design, but also for practical applications such as automotive emission control and fuel cells. In this study, by coupling the competitive gaseous adsorptions and multiple reaction pathways via a state-to-state microkinetic formalism, we reveal CO oxidation mechanisms on small Pd ensembles under realistic experimental conditions. It is found that reaction of O-2 with preadsorbed CO on adjacent Pd sites is the dominant pathway at low temperatures (denoted as the preadsorbed CO oxidation pathway, or PCOP). As the temperature increases, different PCOPs dominate CO oxidation. At even higher temperatures, the CO oxidation reaction proceeds primarily via the recombination of dissociated O atoms and CO (denoted as the dissociated O-2 pathway, or DO2P). Among different ensembles investigated, the Pd dimer possesses the best low-temperature CO oxidation activity, while the tetramer outperforms other forms at higher temperatures. It is concluded that oxygen adsorption ability is the main factor influencing the reactivity. This work unravels the intrinsic activity of the catalyst on the microscopic scale and shed light on ensemble engineering for maximizing its reactivity. (C) 2019 Elsevier Inc. All rights reserved.