To assess the control of corneal hydration in patients with diabetes during a contact lens-induced hypoxia. Corneal stress was induced in 15 patients with diabetes and 23 healthy patients by having them wear contact lenses for 2 hours. Pachymetries were measured and corneal parameters (percentage recovery per hour [PRPH], time for deswelling [T99%] and induced swelling [IS]) were calculated. In the mean time, tears were collected to assess the activity of lactate dehydrogenase (LDH), and a specular microscopy (SM) was performed. In patients with diabetes, PRPH, T99%, and LDH activity were statistically significantly modified (p < 0.05), whereas IS and SM were not. This decreased ability to recover the initial corneal thickness after a transient edema caused by hypoxia confirms the enzymatic dysfunction of the endothelial pumps that are partly caused by a shift toward anaerobic metabolism.