31P image selected in vivo spectroscopy was used to measure deep grey matter intracellular pH in 43 neonates with hypoxic-ischaemic encephalopathy. All neonates had previously received therapeutic hypothermia, the current standard of care. Brain alkalosis was associated with poor outcomes reproducing what was found from whole-brain pH measurements in the pre-cooling era. Brain alkalosis was associated with increased seizure burden, the first time this has been shown in babies. Avoiding brain alkalosis could be a new objective for treating seizures and for neuroprotection in neonatal encephalopathy.