Sleep deprivation (SD) refers to the sleep deprivation caused by the outside world or its own reasons. SD has profound impacts on both physical and mental health. There is a growing concern about its impact on cognitive function, but its related mechanisms are still unclear and there is a lack of safe and effective treatment methods. Orexin is a neuropeptide produced by the hypothalamus and mainly plays a role in the central system. In recent years, it has been found to exert a wide range of effects on the regulation of food intake, sleep cycles, and cognition. This review explores the possible mechanisms of orexin in sleep and learning memory, providing a new perspective for the mechanism exploration and clinical treatment of SD‑related cognitive dysfunction.