Removing CO from hydrogen streams is an important industrial process. The catalytic preferential oxidation of CO (PrOx) is a promising method for CO removal, leaving the hydrogen concentration unchanged. Here, the effect of size and support on the gold-catalyzed PrOx reaction using size-controlled Au nanocrystals (NCs) is investigated. For all supports, Au NC sizes of 2-5 nm show the highest rates, whereas for larger sizes rates drop. Ceria-supported Au shows by far the best performance. By analyzing the dependency of the reaction rate on the NC diameter, the most active centers for CO oxidation on Au/CeO 2 are Au 1 corner atoms at the interface with the support, resulting in 2.1 nm Au NCs supported on ceria reaching full O 2 conversion and CO selectivity of about 50%. Therefore, it is suggested that increasing the fraction of Au-ceria interface sites would lead to the best performing materials for this reaction.