Changes in electroencephalography (EEG) voltage range are used to monitor the depth of anaesthesia, as well as predict outcome after hypoxia-ischaemia in neonates. Xenon is being investigated as a potential neuroprotectant after hypoxic-ischaemic brain injury, but the effect of Xenon on EEG parameters in children or neonates is not known. This study aimed to examine the effect of 50% inhaled Xenon on background amplitude-integrated EEG (aEEG) activity in sedated healthy newborn pigs.Five healthy newborn pigs, receiving intravenous fentanyl sedation, were ventilated for 24 h with 50%Xenon, 30%O2 and 20%N2 at normothermia. The upper and lower voltage-range of the aEEG was continuously monitored together with cardiovascular parameters throughout a 1 h baseline period with fentanyl sedation only, followed by 24 h of Xenon administration.The median (IQR) upper and lower aEEG voltage during 1 h baseline was 48.0 μV (46.0-50.0) and 25.0 μV (23.0-26.0), respectively. The median (IQR) aEEG upper and lower voltage ranges were significantly depressed to 21.5 μV (20.0-26.5) and 12.0 μV (12.0-16.5) from 10 min after the onset of 50% Xenon administration (p=0.002). After the initial Xenon induced depression in background aEEG voltage, no further aEEG changes were seen over the following 24h of ventilation with 50% xenon under fentanyl sedation. Mean arterial blood pressure and heart rate remained stable.Mean arterial blood pressure and heart rate were not significantly influenced by 24h Xenon ventilation. 50% Xenon rapidly depresses background aEEG voltage to a steady ~50% lower level in sedated healthy newborn pigs. Therefore, care must be taken when interpreting the background voltage in neonates also receiving Xenon