Solution (17)O-NMR application to biological macromolecules is extremely limited. We describe here (17)O-NMR observation of the (17)O(2)-oxidized cysteine side chain of human Cu,Zn-superoxide dismutase in solution using selective (17)O(2) oxidation. (17)O-NMR with the aid of (17)O-labeling has wide potential to probe the environment and dynamics of oxidizable functionalities in proteins.