This study aimed to investigate the effect of a single night of continuous positive airway pressure (CPAP) treatment on spontaneous brain activity and the underlying neuropathological mechanisms in patients with severe obstructive sleep apnea (OSA). The study involved 30 severe OSA patients and 19 healthy controls (HC). Fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) methods were employed to evaluate spontaneous brain activity in all participants. Following a single night of CPAP treatment, ReHo values increased in the bilateral caudate and decreased in the right superior frontal gyrus. The fALFF values increased in the left orbital part of the middle frontal gyrus and the right orbital of the inferior frontal gyrus (Frontal_Inf_Orb_R). However, fALFF values decreased in the medial part of the left superior frontal gyrus and the right supramarginal part of the inferior parietal lobe. Pearson correlation analysis revealed a positive relationship between the change in the fALFF in the Frontal_Inf_Orb_R and the change in REM sleep duration (r= 0.437,p= 0.016) following a single night of CPAP treatment. We concluded that observing changes in abnormal fALFF and ReHo in OSA patients before and after a single night of CPAP treatment may enhance our understanding of the neurological mechanisms in patients with severe OSA.