<i>Background:</i> Upper airways in patients with obstructive sleep apnea syndrome (OSAS) are more likely narrower than those of normal subjects, a factor in increasing the work of breathing (WOB) in these individuals. <i>Objectives:</i> To evaluate WOB while sitting and while supine, both awake and during stage 2 sleep, in patients with hypercapnic or eucapnic OSAS. <i>Method:</i> Twenty normal control subjects without OSAS, 20 patients with eucapnic moderate or severe OSAS and another 8 patients with hypercapnic severe OSAS were studied. WOB was measured by esophageal manometry with the subjects seated and then with the subjects supine, both while awake and during stage 2 sleep. <i>Results:</i> In both the control and the eucapnic group, WOB was normal in the sitting position. When the eucapnic subjects lay supine, their WOB increased, both while awake and asleep. In contrast, the hypercapnic subjects had an abnormally high WOB both sitting and supine, whether awake or asleep. <i>Conclusion:</i> WOB was increased in subjects with hypercapnic OSAS in both the sitting and supine positions. While eucapnic individuals with OSAS have increased WOB when supine, it is normal when they are sitting upright.