Recently, high flow oxygen therapy (HFOT) is becoming more popular in the treatment of any kind of respiratory failure. Pediatric mechanical ventilation consensus conference (PEMVECC) guidelines suggest measuring oxygen saturation by pulse oximetry (SpO2) in all ventilated children and furthermore to measure partial arterial oxygen pressure (PaO2) in moderate‑to‑severe disease in order to prevent excessive use of oxygen while preventing hypoxemia and hyperoxemia. However, from a practical point of view, this may require frequent manual adjustments of the inspired oxygen, which might be unfeasible, especially in high-demand periods, such as the recent COVID19 pandemic. Moreover, the COVID19 pandemic has also highlighted the need for optimizing oxygen usage at the hospital level, since medical oxygen can become a scarce resource in high-demand periods, such as a pandemic. Two proof-of-concept studies showed that automatic oxygen titration (AOT) is feasible in patients receiving high flow nasal oxygen therapy (HFNT) in an exercise-induced desaturation model and in patients with mild acute hypoxemic respiratory failure. This study aims to compare the safety and efficacy of a closed- loop FiO2 controller with conventional manual control of FiO2 during HFOT of pediatric patients in a pediatric intensive care unit (PICU). The hypothesis of this study is: Close-loop FiO2 controller increases the time spent within clinically targeted SpO2 ranges and decreases the time spent outside clinical target SpO2 ranges as compared to manual oxygen control in PICU patients treated with HFOT. This study was registered to clinical trials with the registration number NCT05032365.