Because 31P NMR (phosphorus-31 nuclear magnetic resonance) spectroscopy can detect phosphorus metabolites and more than 90% of them reside in corneal epithelium, we applied this technique to the examination of the metabolic response of the cornea (epithelium) to soft contact lens (CL) wear. Our results showed that 4 h of soft CL (59% water) wear caused a 50% loss of ATP, and both ATP and phosphocreatine (PCr) decreased drastically if the eyes were closed. Topical application of 5.5 mM glucose to CL-fitted eyes restored the 31P profile to nearly normal. Possible approaches for maintaining corneal health are discussed.