The present study aimed to assess the effect of a conservative (permissive hypoxemia) versus conventional (normoxia) protocol for oxygen supplementation on the outcome of type I respiratory failure patients admitted to respiratory intensive care unit (ICU). This randomized controlled clinical trial was carried out at the Respiratory ICU, Chest Department of Zagazig University Hospital, for 18 months, starting in July 2018. On admission, 56 enrolled patients with acute respiratory failure were randomized in a 1:1 ratio into the conventional group [oxygen therapy was supplied to maintain oxygen saturation (SpO2) between 94% and 97%] and the conservative group (oxygen therapy was administered to maintain SpO2 values between 88% and 92%). Different outcomes were assessed, including ICU mortality, the need for mechanical ventilation (MV) (invasive or non-invasive), and ICU length of stay. In the current study, the partial pressure of oxygen was significantly higher among the conventional group at all times after the baseline reading, and bicarbonate was significantly higher among the conventional group at the first two readings. There was no significant difference in serum lactate level in follow-up readings. The mean duration of MV and ICU length of stay was 6.17±2.05 and 9.25±2.22 days in the conventional group versus 6.46±2.0 and 9.53±2.16 days in the conservative group, respectively, without significant differences between both groups. About 21.4% of conventional group patients died, while 35.7% of conservative group patients died without a significant difference between both groups. We concluded that conservative oxygen therapy may be applied safely to patients with type I acute respiratory failure.