Obstructive sleep apnea syndrome (OSA), characterized by chronic intermittent hypoxia (CIH), is linked to cognitive impairment and neuronal damage. Leptin, a peptide hormone involved in energy metabolism, has shown neuroprotective effects in various neurological disorders, yet its role in CIH-induced cognitive impairment remains unclear. This study used a CIH mouse model to investigate the effects of leptin on cognitive function and neuronal damage, with a particular focus on Sirtuin 1 (SIRT1) as a potential molecular mediator. Mice were exposed to CIH and treated with leptin, with or without a SIRT1 inhibitor. Cognitive performance was assessed using the Morris Water Maze (MWM) and Y-maze tests. Neuronal damage was evaluated by H&E and Nissl staining, while oxidative stress was measured by Reactive Oxygen Species (ROS) and malondialdehyde (MDA) levels, and Superoxide Dismutase (SOD) activity. SIRT1 expression was determined via western blot analysis. Leptin treatment significantly improved cognitive performance in CIH mice, evidenced by reduced escape latency, increased platform crossings in the MWM, and enhanced alternation rates in the Y-maze. Additionally, leptin mitigated CIH-induced neuronal damage and oxidative stress, demonstrated by improved neuronal structure and reduced ROS and MDA levels. These benefits were associated with increased SIRT1 expression, whereas SIRT1 inhibition reversed leptin's positive effects, highlighting the crucial role of SIRT1 in mediating leptin's neuroprotective effects. These findings suggest that leptin alleviates CIH-induced cognitive dysfunction and neuronal damage through SIRT1 upregulation, offering insights into potential therapeutic mechanisms and future clinical applications.