Normal sleep and sleep-wake cycle are critical for cognitive functions such as learning and memory, while sleep deprivation (SD) impairs learning and memory through a variety of mechanisms, in which memory consolidation function of rapid eye movement (REM) sleep and synaptic plasticity play a critical role. In recent years, studies have shown that melanin-concentrating hormone (MCH) system plays an essential role in learning and memory impairment induced by sleep deprivation. This review summarizes the changes of MCH system function in sleep deprivation, its effect on REM sleep and synaptic plasticity, and how it affects learning and memory function, so as to provide new ideas for further exploring the mechanism of learning and memory impairment of sleep deprivation.