Background: Systemic inflammation, neurocognitive impairments, and morphologic brain changes are associated with obstructive sleep apnea (OSA). Understanding their longitudinal evolution and interactions after surgical treatment provides clues to the pathogenesis of cognitive impairment and its reversibility. In the present study, we investigate clinical disease severity, systemic inflammation, cognitive deficits, and corresponding gray matter volume (GMV) changes in OSA, and the modifications following surgery. Methods: Twenty-one patients with OSA (apnea-hypopnea index, AHI > 5) and 15 healthy volunteers (AHI < 5) underwent serial evaluation, including polysomnography, flow cytometry for leukocyte apoptosis categorization, cognitive function evaluation, and high-resolution brain scan. Disease severity, leukocyte apoptosis, cognitive function, and imaging data were collected to assess therapeutic efficacy 3 months after surgery. Results: Pre-operatively, patients presented with worse cognitive function, worse polysomnography scores, and higher early leukocyte apoptosis associated with increased insular GMV. There was reduced GMV in the anterior cingulate gyrus before and after surgery in the cases compared to that in controls, suggesting an irreversible structural deficit. Post-operatively, there were significant improvements in different cognitive domains, including attention, executive and visuospatial function, and depression, and in early leukocyte apoptosis. There was also a significant decrease in GMVs after treatment, suggesting recovery from vasogenic edema in the precuneus, insula, and cerebellum. Improvement in early leukocyte apoptosis post-surgery predicted better recovery of precuneus GMV. Conclusions: In OSA, increased disease severity and systemic inflammation can alter GMV in vulnerable regions. Surgical treatment may improve disease severity and systemic inflammation, with subsequent recovery in brain structures and functions.