Objective To study the effect of oxygen therapy by different flow on pulse arterial oxygen saturation (SpO₂) of postoperative patients of general anesthesia in high altitude area. Methods Eighty cases with operation under general endotracheal anesthesia were enrolled in the study between August 2017 and April 2018 in Ali district People's Hospital of Tibet. By random number table, the patients were divided into 4 groups according to oxygen flow after extubation including 2 L/min (group L₁), 4 L/min (group L₂), 6 L/min (group L₃) and 8 L/min (group L₄). SpO₂ was recorded as baseline before operation without oxygen inhalation and 30 min, 1 h, 2 h, 4 h or 24 h later after oxygen inhalation with oral and nasal mask ventilation. Results There were 47 male and 33 female cases with age range 19-58 years and weight 48-72 kg. The level of American Association of Anesthesiologists was grade Ⅰ-Ⅱ preoperatively. All the SpO₂ of cases was higher by oxygen therapy with oral and nasal mask after extubation of general anesthesia than before surgery (P< 0.05). SpO₂ remained lower level at oxygen flow 2 L/min and was close to healthy people in low altitude areas at 4 L/min. However, SpO₂ increased no longer when oxygen flow increased to 6 L/min or more. There was no significant difference in oxygen saturation between group L₂ and group L₃ and between group L₂ and group L₄ (P> 0.05) after 4 hours of intake oxygen. Therefore oxygen flow could be reduced to 4 L/min. When patients intaked oxygen for 24 h after surgery, SpO₂ in group L₁ was 94.86% which is close to 95% the SpO₂ of healthy people. We recommended that oxygen flow could be reduced to 2 L/min 24 h later. Conclusions Early oxygen intake in patients with general anesthesia in high altitude areas need 6 L/min of oxygen flow or more. Thereafter, it can be reduced to 4 L/min and 2 L/min for avoiding the waste of high flow oxygen and the risk of oxygen poisoning.