The interaction of metal nanoparticles with oxide supports in heterogeneous catalysis has been intensely discussed for decades because the support may change the surface properties and electronic structure of the nanoparticles(1-5). To understand support-induced phenomena is key for the design of advanced materials. Here we demonstrate a long-range effect of metal/oxide boundaries on the reactivity of Pd in CO oxidation. The effect was observed directly by photoemission electron microscopy (PEEM) and rationalized by density functional theory (DFT) calculations. We show that the higher CO tolerance of sites at the nanoscale perimeter of the metal/oxide interface makes entire micrometre-sized Pd particles more resistant to CO poisoning. This is attributed to the critical role of the perimeter sites for the initiation of deactivation and reactivation fronts, which were used to probe the metal/oxide interface effect. This finding should affect the quest for better CO oxidation catalysts, a hot topic for automotive stopstart systems and hybrid vehicles(6,7).