Orexins have previously been shown to promote wakefulness, regulate lipid metabolism and participate in energy homeostasis. The aim of the study was to determine the relationship between plasma orexin-A and body composition in COPD in-patients with hypercapnic respiratory failure. 40 patients with hypercapnic respiratory failure and 22 healthy individuals were enrolled prospectively in this study. Plasma orexin-A levels, BMI, SaO(2), PaCO(2) and PaO(2) were noted for all the patients. Plasma orexin-A levels were higher in the underweight (UW) group, normal weight (NW) group and overweight (OW) group of COPD patients as compared with UW, NW and OW group of the control group (P < .05). Plasma orexin-A in COPD patients were higher in the OW group than in the NW group and the UW group. Plasma orexin-A levels showed significant correlation with body mass index (BMI), independent of PaO(2) (r = 0.576; P < .05) and %fat (r = 0.367; P < .05); a negative correlation was noted between plasma orexin-A levels and PaO(2) (r = -0.738; P < .05) and SaO(2) (r = -0.616; P < .05). Our results suggest that orexin-A levels are high in COPD patients with hypercapnic respiratory failure, and vary according to BMI and body composition. Orexin-A may be associated with the severity of hypoxemia in COPD patients with hypercapnic respiratory failure.