Cytochrome c oxidase is the terminal enzyme of the mitochondrial (mt) respiratory chain. It contains copper ions, which are organized in two centres, Cu-A and Cu-B. The Cu-A site of subunit Cox2p is exposed to the mt intermembrane space, while the Cu-B site of subunit Cox1p is buried in the inner mt membrane. Incorporation of copper into the two centres is crucial for the assembly and activity of the enzyme. Formation of the Cu-B site is dependent on Cox11p, a copper-binding protein of the mt inner membrane. Here, we experimentally prove that Cox11p possesses a N-in-C-out topology, with the C-terminal copper-binding domain exposed in the mt intermembrane space. Furthermore, we provide evidence for the association of Cox11p with the mt translation machinery. We propose a model in which the Cu-B site is co-translationally formed by a transient interaction between Cox11p and the nascent Cox1p in the intermembrane space.