Cytochrome c oxidase (COX) is a multi-subunit terminal oxidase of the eukaryotic respiratory chain involved in the reduction of oxygen to water. Numerous lines of evidence suggest that the assembly of COX is a multi-step, assisted process that depends on several assembly factors with largely unknown functions. Sco1/2 proteins have been isolated as high-copy number suppressors of a deletion of copper chaperone Cox 17, implicating Sco1/2 in copper transport to COX subunits I or II. Here I report the similarity of Sco1/2 assembly factors to peroxiredoxins and thiol:disulfide oxidoreductases with a thioredoxin fold, suggesting that Sco-related proteins perform a catalytic rather than a copper transport function. Reported sequence similarities, together with the functional role of bacterial Sco-related proteins suggest that Sco-related proteins represent a new class of membrane-anchored thiol:disulfide oxidoreductases involved in COX maturation.