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Elevated carbon dioxide (CO2) blood levels have a depressant effect on the central nervous system and can lead to coma in adults. Less is known about the effect of CO2 on the neurological function of infants.To describe the effect of acute severe hypercapnia (PaCO2 >70 mm Hg) on amplitude-integrated electroencephalography (aEEG) and cerebral oxygenation in newborn infants.Observational study of full-term and preterm infants with acute severe hypercapnia (identified by arterial blood gas measurements), monitored with aEEG. Visual analysis of the aEEG was performed in all infants. In preterm infants <32 weeks postmenstrual age (PMA), analysis of two-channel EEG was performed. Mean spontaneous activity transients (SAT) rate (SATs/min), interval between SATs (ISI in seconds) and the ISI percentage (ISP) were calculated for 10-min periods before, during and after hypercapnia. Mean regional cerebral oxygen saturation (rScO2) and fractional tissue oxygen extraction (FTOE) measured with near-infrared spectroscopy were also calculated for these periods.Twenty-five infants (21 preterm, 4 full-term) comprising 32 episodes of acute severe hypercapnia were identified. Twenty-seven episodes were accompanied by a transient aEEG depression. Twenty-two episodes in 15 preterm infants <32 weeks PMA were quantitatively analysed. During hypercapnia, SAT rate decreased and ISI and ISP increased significantly. No significant change occurred in rScO2 or FTOE during hypercapnia.Profound depression of brain activity due to severe hypercapnia is also seen in infants. It can be recognised by an acute depression of the aEEG, without clinically detectable changes in cerebral oxygenation.