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Objective The aim of this study was to determine the prevalence, outcomes and risk factors for intraoperative desaturation in neonates undergoing non-cardiac surgery.Methods This retrospective study included neonates who underwent non-cardiac surgery between April 2020 and October 2022. Patients were classified as normal or reduced oxygenation based on a review of their medical records and whether they experienced intraoperative desaturation. The incidence of intraoperative desaturation, as well as postoperative outcomes and other characteristics, was recorded.Results A total of 1005 neonates were included, of whom 118 (11.74%) experienced intraoperative desaturation. Intraoperative desaturation was significantly associated with increased postoperative mortality (16.95% vs. 4.62%, p<0.001) and postoperative outcomes including pulmonary complications, acidosis, anemia, thrombocytopenia, unplanned surgery and intubation along with prolonged hospital and intensive care unit stay (all p<0.05). After conducting both univariate and multivariate analyses, 10 preoperative and surgical factors were identified to be significantly associated with intraoperative desaturation. These included six preoperative disease and treatment factors (pneumonia, pulmonary arterial hypertension, anemia, acidosis, pulmonary surfactant treatment and oxygen therapy), two surgical factors (duration of surgery and thoracic surgery) along with the American Society of Anesthesiologists physical status and low weight.Conclusions The incidence of intraoperative desaturation among neonatal patients is relatively high, and it may be associated with a multitude of serious adverse complications. Several perioperative factors are significantly associated with the occurrence of intraoperative desaturation.