Although the risks associated with extended wear contact lenses are well-known, there has not been an adequate explanation of why sleeping with the lenses on increases the risk of infection. It is contended that the reduction in the available oxygen caused by contact lenses does not in itself explain the high rate of corneal infection caused by wearing the lenses while sleeping. This paper examines the contribution that the mechanism of sleep itself makes to the risk of infection, based on patient studies in two optometric practices. The results show that the risk of ocular infection, particularly corneal ulcers, is substantially increased with overnight wear of lenses. A review of the role of oxygen deprivation, atmospheric pollution, bacterial survival strategies, infection-resistant defenses during wakefulness, and patterns of sleep indicates that oxygen deprivation of the cornea is not the only factor in the increased risk associated with wearing the lenses while sleeping. It is suggested that the combination of the introduction of airborne pollutants to the contact lens during the day, the reduced oxygen transmission through contact lenses and closed lids, and the lack of eye and lid movement during sleep together create the conditions in which bacterial infection is most likely to occur.