STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with an increasing risk of cognitive impairment, but traditional hypoxic indicators can not accurately identify cognitive impairment. This study aimed to assess a new indicator, hypoxic burden, in cognitive impairment in OSA. METHODS: A total of 116 patients with OSA were enrolled in this study. Daytime sleepiness and cognition were assessed using the Epworth Sleepiness Scales and Montreal Cognitive Assessment (MoCA), respectively. All participants underwent polysomnography (PSG). The hypoxic burden was derived from PSG and calculated according to a specific algorithm. All the participants were divided into two groups. Seventy-seven were OSA with mild cognitive impairment (OSA + MCI), and 39 were OSA without mild cognitive impairment (OSA-MCI). The relationship between hypoxic burden and cognitive impairment was analyzed by establishing a series of logistic regression models. RESULTS: Hypoxic burden was higher in OSA + MCI group compared with OSA-MCI group, while there was no significance found for the apnea-hypopnea index between the two groups. After adjusting for various confounders, patients with OSA who had a higher total hypoxic burden and rapid eye movement-hypoxic burden in the fourth quartile were found to have an increased risk of MCI compared to those in the first quartile. The adjusted ORs were 7.69 (95% CI, 1.15 to 51.55) and 8.87 (95% CI, 1.22 to 64.34), respectively. However, There was no significant association between the other traditional hypoxic parameters and cognitive function after adjusting for various confounders. CONCLUSIONS: Compared to the conventional hypoxic parameter, a higher hypoxic burden is associated with cognition and may be an important indicator for assessing MCI in OSA.