Background/aim: One of the more difficult ventilator problems confronting physicians in the critical care unit is the management of patients who have unilateral lung disease (ULD) . This study was conducted to investigate the efficacy of manual hyperinflation (MHI) in supine position on arterial partial pressure of oxygen (PaO2) and arterial oxygen saturation (SaO2) in those patients. Materials and methods: Totally, 20 patients (men) with unilateral lung diseases and their ages ranged from 40 to 50 years were recruited .The patients were selected from Kasr El-Aini Hospitals (intensive care unit) and all patients received manual hyperinflation (MHI) from supine position in addition to routine chest physiotherapy for 15 min for each session two sessions per day for three consecutive days. Outcomes: PaO2 and SaO2 were assessed before the 1st morning session (Pre 1) and after the 5TH morning session (Post) of manual hyperinflation (MHI) and chest physiotherapy to subside any drug interactions on ABG results at night session. Results: After sessions, significant improvements of PaO2 and SaO2 were obtained in the post measurement compared with that at the beginning of the sessions. Conclusion: It was concluded that the physiological effect of the manual hyperinflation from supine lying position showed significant improvement on PaO2 and SaO2 in mechanically ventilated patients with unilateral lung disease (ULD).