Objective To evaluate the correlation of vascular endothelial growth factor (VEGF) and vascular endothelial cadherin (VE-Cadherin) in serum with the severity of obstructive sleep apnea (OSA) and explore their clinical value in OSA. Methods A total of 90 patients with OSA admitted to the Sleep Monitoring Center of the Affiliated Hospital of Xuzhou Medical University from April 2023 to June 2024 were prospectively selected. Based on the apnea-hypopnea index (AHI), the patients were divided into a mild group (5 - 15 times/hour, n=30), a moderate group (>15 - 30 times/hour, n=28), and a severe group (>30 times/hour, n=32). Thirty healthy individuals who underwent physical examinations during the same period were included as a control group. The levels of serum VEGF and soluble VE-Cadherin (sVE) in all subjects were detected by enzyme-linked immunosorbent assay. The differences in serum VEGF and sVE levels among the groups were compared, and the correlations between serum VEGF and sVE levels and sleep parameters were explored. The moderate and severe OSA patients were given 3 months of continuous positive airway pressure (CPAP) treatment, and the changes in sleep parameters and serum VEGF and sVE levels before and after treatment were compared. Results The levels of serum VEGF and sVE in the OSA patients increased with the severity of the disease; the levels of serum VEGF and sVE in the moderate and severe OSA groups were significantly higher than those in the healthy control group and the mild OSA group (P<0.05). The levels of serum VEGF and sVE in the severe OSA group were significantly higher than those in the moderate OSA group (P<0.05). There was no significant difference in the expression levels of serum VEGF or sVE between the mild OSA group and the healthy control group (P>0.05). The sensitivity and specificity of serum VEGF in diagnosing OSA were 65.6% and 93.3%, respectively, with an area under curve (AUC) value of 0.845. The sensitivity and specificity of serum VE-Cadherin in diagnosing OSA were 64.4% and 96.7%, respectively, with an AUC value of 0.835. After 3 months of CPAP treatment, AHI, longest apnea time, serum VEGF and sVE levels in the moderate and severe OSA groups decreased significantly, mean arterial oxygen saturation and lowest arterial oxygen saturation increased significantly (P<0.05). Conclusions The levels of VEGF and VE-Cadherin in serum of OSA patients are significantly elevated and positively correlated with the severity of OSA. Monitoring the changes in the levels of VEGF and VE-Cadherin in serum of OSA patients is helpful for evaluating the therapeutic effect of CPAP.