Abstract: Objective To investigate the correlations of serum amyloid-β (Aβ) and α-enolase (ENO1) levels with disease severity and hypoxia indices in patients with obstructive sleep apnea (OSA), and to evaluate their clinical significance.Methods A total of 66 OSA patients who were diagnosed by polysomnography (PSG) at the Sleep Center of the Affiliated Hospital of Xuzhou Medical University from January to August 2024 were enrolled. According to the apnea-hypopnea index (AHI), the patients were categorized into mild (n=22), moderate (n=21), and severe (n=23) groups. Meanwhile, 21 healthy individuals undergoing routine health examinations were included as a control group. Their general data and clinical information and OSA severity were collected. Serum Aβ and ENO1 levels were measured by ELISA. Correlations between Aβ/ENO1 and PSG parameters and OSA severity were analyzed, and diagnostic performance of serum Aβ and ENO1 for OSA was evaluated.Results Compared with the control group, serum Aβ and ENO1 levels significantly increased in the OSA group(P<0.05). Correlation analysis showed that both Aβ and ENO1 were positively correlated with AHI, and negatively correlated with mean oxygen saturation (MSaO₂) and lowest oxygen saturation (LSaO₂) (all P<0.05). ENO1 was also positively correlated with the longest apnea time (LAT) (r=0.240,P<0.05). Multivariable logistic regression indicated that elevated ENO1 was an independent influencing factor for OSA (OR=1.034, P=0.012). Receiver operating characteristic (ROC) curve analysis showed that the areas under the curve (AUCs) for serum Aβ, ENO1, and their combination in diagnosing OSA were 0.734, 0.702, and 0.745, respectively.Conclusions Serum Aβ and ENO1 levels are closely associated with OSA severity and nocturnal hypoxia and demonstrate potential value as auxiliary diagnostic biomarkers, suggesting that they may be involved in the pathophysiological processes related to OSA.