Excessive daytime sleepiness, the most prevalent symptom associated with the OSAS, is hypothesized to result from either fragmentation of sleep or hypoxemia during sleep. Measures of nocturnal sleep, respiration during sleep, and daytime sleepiness in 466 patients with apnea were collected to evaluate these two hypotheses. The various parameters were submitted to correlation and multiple regression analyses to predict daytime sleepiness as measured by the MSLT. The RAI, which measures the number of arousals from sleep associated with respiratory disturbances (best fragmentation correlation), produced a higher correlation with MSLT scores than did TMES (best hypoxemia correlation); however, the measures were highly intercorrelated, and multiple regression analyses to determine which parameters independently predicted MSLT showed the single best predictor to be the RAI. Additional independent variance in MSLT score was explained by TST and PSG1. Measures of hypoxemia provided little or no independent predictive information. These data support the hypothesis that sleep fragmentation is an important determinant of daytime sleepiness in patients with apnea.