The etiology of excessive daytime sleepiness in patients with sleep-disordered breathing (SDB) is not well defined. In this study, we examined the relationships between several clinical and polysomnographic parameters and the degree of hypersomnolence in 741 patients with SDB (apnea-hypopnea index [AHI] >/= 10 events/h). The study sample was obese (body mass index [BMI]: 35.3 +/- 8.5 kg/m2) and had evidence of moderate SDB (AHI: 47.6 +/- 29.3 events/h). Hypersomnolence was quantified with the multiple sleep latency test (MSLT) and survival analysis was used to assess the risk factors for hypersomnolence. In a multivariate proportional hazards model, AHI and nocturnal hypoxemia were independent predictors of hypersomnolence (MSLT < 10 min). The adjusted relative risks (RR) of hypersomnolence were 1.00, 1.30, and 1.65 for patients with an AHI of 10 to 29.9, 30 to 59.9, and >/= 60 events/h, respectively. A positive association between hypersomnolence and oxyhemoglobin desaturation (DeltaSaO2) was observed with RR of 1.00, 1.18, 1.43, and 1.94 for a DeltaSaO2 of </= 5%, 5.1 to 10%, 10.1 to 15%, and > 15%, respectively. Sleep fragmentation, as assessed by the distribution of sleep stages, was also an independent predictor of hypersomnolence. Using stage 1 sleep as a reference, an increase in stage 2 and slow wave sleep (SWS) were protective from hypersomnolence. For a 10% increase in stage 2 or SWS the adjusted RR for hypersomnolence were 0.93 and 0.79, respectively. REM sleep showed no significant association with the degree of hypersomnolence. These results suggest that AHI, nocturnal hypoxemia, and sleep fragmentation are independent determinants of hypersomnolence in SDB.