Although the specific functions of sleep are not known, an increasing body of literature has suggested that sleep is important for the proper functioning of host defense systems. Sleep loss is associated with changes in some parameters of host defense, whereas pathogenic challenge leads to alterations in sleep patterns, probably mediated by activation of host defense systems. However, whether sleep-host defense relationships represent physiologically important regulatory interactions vs. nonspecific cross-reactivity between the two systems remains an open question. In either case, it is unlikely that sleep or sleep loss have global effects on host defenses or vice versa. Further work is needed to understand the role of sleep in health and disease.