Nocturnal hypoxemia is associated with excessive daytime sleepiness in patients with chronic respiratory disease. This relationship has not been explored in patients with cancer. This study examined the prevalence of nocturnal hypoxemia in patients admitted to a specialist palliative care unit, and explored relationships with demographic and physiological parameters, opioid or other sedative drug use, and daytime sleepiness, fatigue, and quality of life. Demographic details, diagnosis, performance status, body mass index, opioid or other sedative drug use, hemoglobin, spirometry, and sniff nasal inspiratory pressures were obtained, along with Epworth Sleepiness Scale, Multidimensional Fatigue Inventory, and Short Form-36 health questionnaire scores. An oximeter recorded resting daytime oxygen saturation (SaO2); overnight SaO2 was recorded for a minimum of five hours. Nocturnal hypoxemia was defined as SaO2<90% for >or=2% of the monitored nighttime. Of 100 patients, 35 had nocturnal hypoxemia. These were more likely to have lung disease (P<0.05), a lower forced expiratory volume in one second % predicted (P=0.01), lower daytime SaO2 (P=0.01) and higher levels of mental fatigue (difficulty concentrating) (P=0.02), compared to those without nocturnal hypoxemia. Both groups exhibited abnormal levels of daytime sleepiness. Nocturnal hypoxemia is common in this group of patients and may contribute to mental fatigue (difficulty concentrating).