SentriO Oxy™ is a newly available, Food and Drug Administration-approved oxygenation mask system that provides high oxygenation, even on low-flow (5–10 L/min) oxygen. This study aimed to accurately measure the intratracheal fraction of inspired oxygen (FiO2) using SentriO Oxy™ masks under relatively low oxygen flow rates. A manikin-ventilator-test lung simulation system was used. We measured FiO2 at the level of the carina, 5 minutes after applying 45 different respiratory parameter combinations using SentriO Oxy™ masks. Tidal volume (TV) was set to 300, 500, and 700 mL; respiratory rate (RR) was set to 8, 12, 16, 20, and 24 breaths per minute; and oxygen flow rate was set to 6, 8, and 10 L/min. Our hypothesis was that FiO2 would be proportional to the difference between oxygen flow rate and minute ventilation. FiO2 measured by smaller TV, lower RR, or higher oxygen flows revealed a significantly higher value, confirming our hypothesis. In addition, using linear regression analysis, we found that TV, RR, and oxygen flow were all significant factors influencing the measured FiO2. Our experiment proposed two prediction equations considering the oxygen flow rate, TV, and RR. The results of our study may provide information and prediction of FiO2 for clinicians to use SentriO Oxy™ masks during sedative anesthetic procedures under low oxygen flow rates.