Purpose: The aim of this study was to evaluate whether sleep deprivation can induce degenerative changes in rat sublingual glands. Methods: For this purpose, a total of 24 males were distributed into three groups: control (n = 8), in which the animals were not subjected to any procedure; sleep deprivation (n = 8) in which the animals were submitted to sleep deprivation for 96 h; recovery (n = 8), in which the animals were subjected to paradoxical sleep deprivation for 96 consecutive hours followed by 96 h without intervention. Morphological changes in sublingual glands as well as the immunoexpressions of some proteins, such as Ki-67, p16, cleaved caspase-3 and BCL-2 were investigated in this setting. Results: The results showed that paradoxical sleep deprivation induced tissue degeneration as a result of the presence of pyknosis, vacuoles and areas of salivary retention, in the experimental groups. Expression of cleaved caspase 3 and BCL-2 were increased in both sleep deprivation and recovery groups. The analysis of Ki-67 showed an increase in expression only in the recovery group, associated with a decrease in p16 levels. Conclusion: Sleep deprivation can induce a degenerative process in the parenchyma of sublingual gland by means of dysregulation of apoptosis associated with proliferative activity. [ABSTRACT FROM AUTHOR]