Obstructive sleep apnea-hypopnea syndrome (OSAHS) is considered a comorbidity associated with morbid obesity, mainly because of the large neck circumference. Depending on its severity, OSAHS can interfere in many homeostasis systems, for example, the central nervous system (CNS). Neuron-specific enolase (NSE) and S100B protein derived from astrocytes are considered sensitive biochemical markers of cerebral injury. We evaluated serum S100B and NSE levels in this study with the aim of detecting possible cerebral injury as a consequence of OSAHS. This was a transverse study with data from 25 morbidly obese patients with OSAHS. Blood samples were collected before and after polysomnography (PSG) to determine S100B and NSE protein levels. We also analyzed data evaluating depression and excessive daytime sleepiness. S100B levels were higher after [0.029 (0.010-0.199) mg/l] compared to before [0.010 (0.010-0.025) mg/l] on PSG (P = 0.002). S100B levels were expressed as means and IQ25-IQ75. NSE levels did not show significant differences before and after PSG. Our study shows a significant increase in S100B level after PSG compared to before. This suggests that there is a CNS astrocyte reaction because of possible cerebral hypoxemia in morbidly obese patients with OSAHS.