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Background and objective The management and treatment of nociception remain one of the major challenges in anesthesiology, and hemodynamic variations may occur due to inadequate analgesia, which at times can be injurious. Pupillometry is a new noninvasive tool to assess nociception during anesthesia. The amount of pupillary reflex dilation (PRD) is directly proportional to the intensity of nociceptive stimuli and inversely proportional to the opioid dosage. This study aimed to assess the use of pupillometry as reflex pupillary dilatation in response to surgical stimulus in children under general anesthesia and to guide intraoperative opioid consumption. Materials and methods After obtaining approval from the institutional ethics committee and written consent from parents, children with an American Society of Anesthesiology (ASA) classification of I and II and aged 2-12 years who were undergoing surgery under general anesthesia were enrolled in this prospective randomized observational study. General anesthesia was standardized with propofol, sevoflurane, and O 2 and N 2 O (50:50%), and fentanyl administration was guided by pupil diameter changes. The primary outcome was to measure pupillary dilatation in response to pain and fentanyl administration guided by it. Results A total of 72 patients were included in the study. The mean pupil diameter significantly increased after surgical stimulus from 1.37 ±0.87 to 2.40 ±1.95 mm (p<0.001). The heart rate (116.2 ±12.25 to 118.50 ±8.20 beats/minute, p=0.18) and systolic BP (114.60 ±17.73 to 118.50 ±12.25 mmHg, p=0.12) did not change significantly on stimulus. The mean fentanyl consumption was 2.4 ug/kg and the side effects were not remarkable. Conclusion Based on our findings, pain has a significant influence on the pupil dilatation reflex in anesthetized children, and opioid administration based on pupil diameter can be valuable in clinical settings. We recommend the use of pupillometry as a pain index in children undergoing surgery under general anesthesia, and it can be a beneficial tool for assessing intraoperative pain. Newer techniques and developments are required in this field., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Singh et al.)