Obstructive sleep apnea (OSA) is a prevalent and underdiagnosed condition associated with cardiovascular diseases, depression, accidents, and stroke. There is an increasing need for alternative diagnostic tools beyond overnight sleep studies that measure the Apnea/Hypopnea Index (AHI). In this single-center, case-control study, we evaluated serum and plasma concentrations of IL-6, IL-8, IL-10, TNF-α, CRP, and S100B in 80 subjects, including 52 OSA patients (27 moderate [15 ≤ AHI ˂ 30], 25 severe [AHI ≥ 30]) and 28 non-OSA controls (AHI 0-5). Participants with OSA showed approximately 2 times higher median concentrations of CRP in plasma, and IL-6 in serum, as well as 1.3 to 1.7 times higher concentrations of TNF-α and IL-8 in plasma compared with the control group. Receiver Operator Characteristic (ROC) curve analysis was performed to evaluate the predictive capabilities of these serum and plasma biomarkers in distinguishing between the OSA and control groups, revealing varying sensitivity and specificity. In summary, in this study, serum and plasma biomarkers CRP, S100B, IL-6, TNF-α, and IL-8 have been shown to be elevated in patients with OSA, correlated positively with disease severity, age, and BMI. These results support the potential role of these biomarkers in diagnosing OSA, supplementing traditional methods such as overnight sleep studies.