<p>Sleep deprivation (SD) is a prevalent issue in modern society, with profound implications for cognitive function and overall health. Although benzodiazepines are frequently employed to manage sleep disorders, their use is complicated by adverse side effects, notably cognitive impairment. This study investigates the comparative effects of chronic sleep deprivation and diazepam administration on memory, learning, and biochemical markers in male Wistar rats. Eighteen rats were randomly assigned to three groups: a sham group receiving DMSO (diazepam solvent) as a vehicle control, a Diaz group administered diazepam, and a chronic sleep restriction (CSR) group subjected to continuous sleep deprivation and DMSO, each for a duration of three weeks. Cognitive performance was assessed using established behavioral paradigms, specifically the passive avoidance memory test and the novel object recognition test, which evaluate aversive and recognition memory, respectively. Biochemical analyses measured key markers, including total antioxidant capacity, reactive oxygen species (ROS), TNF-α, and BDNF levels in brain tissue, to elucidate underlying molecular mechanisms. Results revealed that both chronic SD and diazepam administration negatively affect learning and memory. However, impairments caused by SD were consistently more severe, affecting both behavioral and molecular parameters. These findings highlight the critical role of adequate sleep in sustaining cognitive health, indicating that while diazepam poses risks to cognitive function, chronic SD constitutes a more substantial threat to brain integrity and performance. This study underscores the urgent need for effective sleep restoration strategies and cautions against the risks of prolonged sleep loss and the unsupervised use of sedative medications.</p>