Objective: To investigate the rate and mechanism of oxygen consumption by the vitreous. Methods: Oxygen consumption was measured with a microrespirometer. Vitreous ascorbate was measured spec-trophotometrically and by gas chromatography-mass spectrometry. Vitreous degeneration was related to the rate of oxygen consumption and ascorbate concentration in samples obtained during vitrectomy. Results: Prolonged exposure to oxygen or treatment with ascorbate oxidase eliminated oxygen consumption by the vitreous. Adding ascorbate restored oxygen consumption. Oxygen consumption persisted after boiling or treating the vitreous with the chelating agents EDTA and deferoxamine. In patients undergoing retinal surgery, liquefaction of the vitreous and previous vitrectomy were associated with decreased ascorbate concentration and lower oxygen consumption. Conclusions: Ascorbate in the vitreous decreases exposure of the lens to oxygen. The catalyst for this reaction is not known, although free iron may contribute. The gel state of the vitreous preserves ascorbate levels, thereby sustaining oxygen consumption. Vitrectomy or advanced vitreous degeneration may increase exposure of the lens to oxygen, promoting the progression of nuclear cataracts. Clinical Relevance: Determining how the eye is protected from nuclear cataracts should suggest treatments to reduce their incidence.