Background: It has been demonstrated that moderate to severe obstructive sleep apnea (OSA) leads to generation of reactive oxygen species and inflammation. We evaluated whether continuous positive airway pressure (CPAP) treatment progressively improves oxidative stress and inflammation, and whether an association exists in severe OSA patients between severity of OSA and biomarkers of oxidative stress and inflammation. Methods:Forty patients with severe OSA (apnea hypopnea index, AHI: 37.8 ± 5.8 /h) that were newly diagnosed using polysomnography were recruited. Patients received CPAP treatment for six months. Patients were assigned to CPAP and non-CPAP treatment groups in equal numbers. The levels of malondialdehyde (MDA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), high sensitivity C-reactive protein (hs-CRP), neutrophils to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) were measured prior to and after three and six months of therapy. Results: AHI was positively correlated with MDA (r = 0.4728, p < 0.01), ALT (r = 0.6081, p < 0.001), AST (r = 0.6299, p < 0.001), NLR (r = 0.3943, p < 0.05), PLR (r = 0.3319, p < 0.05), and hs-CRP (r = 0.5728, p < 0.001). In the CPAP but not in non-CPAP treatment group, MDA, AST, NLR, PLR, and hs-CRP levels (p < 0.001), and ALT (p < 0.05) levels were improved after three and six months of treatment. After six months, MDA levels decreased further compared to MDA levels at three months, and this decrease was significant (p < 0.001). Conclusion: Our study demonstrates that CPAP therapy in severe OSA patients produces clinical benefits by improving oxidative stress and inflammation progressively, and that severity of OSA is correlated with oxidative stress and inflammation.