<b>Background:</b> Obstructive sleep apnea (OSA) is a risk factor for mild cognitive impairment (MCI). However, the evidence to prove the bidirectional causality of this association is insufficient. <b>Objective:</b> To identify potential biomarkers for MCI in patients with OSA.Methods: 103 individuals with moderate-severe OSA diagnosed by polysomnography were recruited and scanned using resting-state functional magnetic resonance imaging (fMRI). Montreal Cognitive Assessment (MoCA) was administered to determine CI.&nbsp;The proteomic biomarkers in the blood samples were quantified using multiplexed bead immunoassays. Multivariate Logistic Regression Model was performed to analyse the association with cognition, neuroimaging, and proteomic biomarkers. <b>Results:</b> Multivariate logistic regression analysis showed statistically significant association between higher Apnea hypopnea index (AHI) and MCI (p=0.040; OR=2.9 CI:1.05-7.8) and between white matter lesions and MCI (p=0.024; OR=3.9 CI:1.19-13.25). Individuals with severe OSA and MCI showed over expression of biomarkers IL-1B (p=0.031; OR= 2.9 CI: 1.10-6.92), APO-A1 (p=0.014; OR=2.4 CI: 1.19-4.95), and APO-J (p=0.013; OR=2.1 CI: 1.17-3.92). <b>Conclusions:</b> These findings suggest roles for proteomic biomarkers in the risk of MCI in individuals with OSA.