Background: Episodes of hyperoxaemia and hypocapnia, which may contribute to b rain injury, occur unintentionally in severely asphyxiated neonates in the first postnatal hours. Objective: To determine whether hyperoxaemia and/or hypocapnia during the first 2 hours of life add to the risk of brain injury after intrapar tum asphyxia. Methods: Retrospective cohort study in term infants with post-asp hyxial hypoxic ischaemic encephalopathy (HIE) born between 1985 and 1995.Severe and moderate hyperoxaemia were defined as PaO2 > 26.6 and PaO2 > 13.3 kPa (20 0 and 100 mm Hg). Severe and moderate hypocapnia were defined as PaCO2 < 2.6 an d PaCO2 < 3.3 kPa (20 and 25 mm Hg). Adverse outcome ascertained by age 24 mont hs was defined as death, severe cerebral palsy, or any cerebral palsy with blind ness, deafness, or developmental delay. With outcome as the dependent variable, multivariate analyses were performed including hyperoxaemic and hypocapnic varia bles, and factors adjusted for initial disease severity. Results: Of 244 infants , 218 had known outcomes, 127 of which were adverse (64 deaths, 63 neurodevelopm ental deficits). Multivariate analyses showed an association between adverse out come and episodes of severe hyperoxaemia (odds ratio (OR) 3.85, 95%confidence interval (Cl) 1.67 to 8.88, p = 0.002), and severe hypocapnia (OR 2.34, 95% Cl 1.02 to 5.37, p = 0.044). The risk of adverse outcome was highest in infan ts who had both severe hyperoxaemia and severe hypocapnia (OR 4.56, 95%Cl 1.4 to 14.9, p = 0.012). Conclusion s: Severe hyperoxaemia and severe hypocapnia were associated with adverse outcom e in infantswith post-asphyxial HIE. During the first hours of life, oxygen sup plementation and ventilation should be rigorously controlled. Background: Episodes of hyperoxaemia and hypocapnia, which may contribute to b rain injury, occur unintentionally in severely asphyxiated neonates in the first postnatal hours. Objective: To determine whether hyperoxaemia and / or hypocapnia during the first 2 hours of life add to the risk of brain injury after intrapar tum asphyxia. Methods: Retrospective cohort study in term infants with post-asp hyxial hypoxic ischaemic encephalopathy (HIE) born between 1985 and 1995. Severe and moderate hyperoxaemia were defined as PaO 2> 26.6 and PaO 2> 13.3 kPa and 100 mm Hg). Severe and moderate hypocapnia were defined as PaCO2 <2.6 an d PaCO2 <3.3 kPa (20 and 25 mm Hg). Adverse outcome ascertained by age 24 mont hs was defined as death, severe cerebral palsy, or any cerebral palsy with blind ness, deafness, or developmental delay. With outcome as the dependent variable, multivariate analyzes were performed including hyperoxaemic and hypocapnic varia bles, and factors adjusted for initial d Of 244 infants, 218 had known outcomes, 127 of which were adverse (64 deaths, 63 neurodevelopm ental deficits). Multivariate analyzes showed an association between adverse out come and episodes of severe hyperoxaemia (odds ratio (OR) 3.85 , 95% confidence interval (Cl) 1.67 to 8.88, p = 0.002), and severe hypocapnia (OR 2.34, 95% Cl 1.02 to 5.37, p = 0.044). The risk of adverse outcome was highest in infan ts who had both severe hyperoxaemia and severe hypocapnia (OR 4.56, 95% Cl 1.4 to 14.9, p = 0.012). Conclusion s: Severe hyperoxaemia and severe hypocapnia were associated with adverse outcom e in infants with post-asphyxial HIE. During the first hours of life, oxygen sup sup plementation and ventilation should be rigorously controlled.