Pulse oximetry and measurement of regional cerebral oxygen saturation (rcSO 2) are used to monitor peripheral and cerebral oxygenation, respectively. However, the response of rcSO 2 and pulse oxygen saturation (SpO 2) to hypoxia in preschool children has not been previously assessed. A total of 36 preschool patients who had undergone a tonsillectomy [age, 4-6 years, American Society of Anesthesiologists grade I or II] were screened and prospectively enrolled in the present study. Hemodynamics, including rcSO 2 , SpO 2 , non-invasive blood pressure, heart rate, electrocardiogram and capnography, were continuously monitored throughout the study. Following pre-oxygenation, pressure-controlled ventilation with 100% oxygen was administered through a mask with a flow rate of 6 l/min, under total intravenous anesthesia, and the end-tidal carbon dioxide partial pressure was maintained between 30 and 40 mmHg. Tracheal intubation was then performed and ventilation was paused until SpO 2 decreased to 90% or rcSO 2 decreased by >10% of the baseline level. The duration from pausing of mechanical ventilation to the start of the rcSO 2 decline was shorter than that of SpO 2 (80.2±23.6 sec vs. 124.4±20.5 sec; P<0.001). Subsequent to the recovery of ventilation, the duration from the starting point to the increasing point of the baseline of rcSO 2 was longer than that of SpO 2 (84.8±24.3 sec vs. 15.2±6.8 sec; P<0.001). From the point where mechanical ventilation was paused to when rcSO 2 /SpO 2 began to decrease, the rcSO 2 and SpO 2 values decreased and a significant correlation of them was observed (Pearson's correlation coefficient=0.317; P=0.027). From the time-point where mechanical ventilation was recovered to the time-point where rcSO 2 or SpO 2 began to increase, rcSO 2 and SpO 2 values decreased and a significant correlation of them was observed (Spearman's correlation coefficient= 0.489; P= 0.006). From the baseline to the minimum value, compared with the SpO 2 , the rcSO 2 declined at a decreased rate (9.7±0.5% vs. 5.3±2.7%; P<0.001). The present clinical trial was registered at http://www.chictr.org.cn on 14th March 2016 (registration no. ChiCTR-OOC-16008095).