Supported AuCu and AuCuPd catalysts were synthesized through the diffusion of Pd and Cu into Au nanoparticle seeds. When supported on SiO2, the AuCuPd nanoparticles were found to be the most active for the oxidation of CO after being exposed to reductive pretreatment conditions as opposed to oxidative pretreatment conditions. In contrast, AuCu/SiO2 was found to be more active for CO oxidation after the alloy phase was segregated into a Au-CuOx heterostructure. In situ XRD and EXAFS were used to monitor the structural changes of AuCu and AuCuPd catalysts as they were subjected to different pretreatment conditions.