Cytochrome c oxidase (CcO) is the terminal enzyme in the respiratory electron transport chain. As part of its catalytic cycle, CcO transfers protons to its Fe-Cu binuclear center (BNC) to reduce oxygen, and in addition, it pumps protons across the mitochondrial inner, or bacterial, membrane where it is located. It is believed that this proton transport is facilitated by a network of water chains inside the enzyme. Here we present an analysis of the hydration of CcO, including the BNC region, using a semi-empirical hydration program, Dowser++, recently developed in our group. Using high-resolution X-ray data, we show that Dowser++ predictions match very accurately the water molecules seen in the D- and K-channels of CcO, as well as in the vicinity of its BNC. Moreover, Dowser++ predicts many more internal water molecules than is typically seen in the experiment. However, no significant hydration of the catalytic cavity in CcO described recently in the literature is observed. As Dowser++ itself does not account for structural changes of the protein, this result supports the earlier assessment that the proposed wetting transition in the catalytic cavity can only either be due to structural rearrangements of BNC, possibly induced by the charges during the catalytic cycle, or occur transiently, in concert with the proton transfer. Molecular dynamics simulations were performed to investigate the global dynamic nature of Dowser++ waters in CcO, and the results suggest a consistent explanation as to why some predicted water molecules would be missing in the experimental structures. Furthermore, in light of the significant protein hydration predicted by Dowser++, the dielectric constant of the hydrated cavities in CcO was also investigated using the Frohlich-Kirkwood model; the results indicate that in the cavities where water is packed sufficiently densely the dielectric constant can approach values comparable even to that of bulk water.