To determine whether upright body position and weight loss would improve daytime gas exchange in moderately obese patients with obstructive sleep apnoea (OSAS), 13 patients with mild or moderate OSAS were studied before and after weight loss. Pulmonary function tests, arterial blood gases and respiratory gas analysis were measured prior to and after a very low calorie diet (VLCD) period of six weeks. Arterial blood gases were measured in supine and standing positions and closing volume in supine and sitting positions before and after weight loss. In the upright position, there was a significant increase in PaO2 (P<0.005) accompanied by a significant decrease in alveolar-arterial PO2 difference (P<0.005) and closing volume (P<0.05). The median weight loss was 11 kg (range 5-18). The number of desaturation episodes (four percentage units or more per hour during sleep) (ODI4) decreased (P<0.01) after weight loss. The change in PaO2 with weight loss correlated with the decrease in ODI4 (r=0.73, P<0.01). The increase in expiratory reserve volume (ERV) was closely related to the amount of weight lost (r=0.895, P<0.01). The results indicate that weight loss and upright body position improved daytime respiratory mechanics and gas exchange in obese patients with OSAS. The findings suggest that obesity plays an important role in the pathogenesis of daytime gas exchange disturbances in obese OSAS patients. The adoption of a more upright sleep posture might improve nocturnal oxygenation in obese patients with OSAS.