<h4>Aims</h4>This study investigated the effects of hydrogen (H<sub>2</sub>) on cognitive impairment in sleep-deprived mice mediated by the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway.<h4>Methods</h4>A chronic sleep deprivation (SD) model was established using the modified multiple platform method, with 18 h of deprivation daily for 28 consecutive days. This evidence concerns the gene HMOX1 and Cognitive impairment.