Understanding the intrinsic catalytic properties of perovskite materials can accelerate the development of highly active and abundant complex oxide catalysts. Here, we performed a first-principles density functional theory study combined with a microkinetics analysis to comprehensively investigate the influence of defects on catalytic CO oxidation of LaFeO 3 catalysts containing single atoms of Rh, Pd, and Pt. La defects and subsurface O vacancies considerably affect the local electronic structure of these single atoms adsorbed at the surface or replacing Fe in the surface of the perovskite. As a consequence, not only the stability of the introduced single atoms is enhanced but also the CO and O 2 adsorption energies are modified. This also affects the barriers for CO oxidation. Uniquely, we find that the presence of La defects results in a much higher CO oxidation rate for the doped perovskite surface. A linear correlation between the activation barrier for CO oxidation and the surface O vacancy formation energy for these models is identified. Additionally, the presence of subsurface O vacancies only slightly promotes CO oxidation on the LaFeO 3 surface with an adsorbed Rh atom. Our findings suggest that the introduction of La defects in LaFeO 3 -based environmental catalysts could be a promising strategy toward improved oxidation performance. The insights revealed herein guide the design of the perovskite-based three-way catalyst through compositional variation.