OBJECTIVE To investigate the impact of new-onset diabetic ketoacidosis (DKA) during childhood on brain morphology and function. RESEARCH DESIGN AND METHODS Patients aged 6-18 years with and without DKA at diagnosis were studied at four time points: < 48 h, 5 days, 28 days, and 6 months postdiagnosis. Patients underwent magnetic resonance imaging (MRI) and spectroscopy with cognitive assessment at each time point. Relationships between clinical characteristics at presentation and MRI and neurologic outcomes were examined using multiple linear regression, repeated-measures, and ANCOVA analyses. RESULTS Thirty-six DKA and 59 non-DKA patients were recruited between 2004 and 2009. With DKA, cerebral white matter showed the greatest alterations with increased total white matter volume and higher mean diffusivity in the frontal, temporal, and parietal white matter. Total white matter volume decreased over the first 6months. For graymatter in DKA patients, total volumewas lower at baseline and increased over 6 months. Lower levels of N-acetylaspartate were noted at baseline in the frontal graymatter and basal ganglia.Mental state scoreswere lower at baseline and at 5 days. Of note, although changes in total and regional brain volumes over the first 5 days resolved, they were associated with poorer delayed memory recall and poorer sustained and divided attention at 6 months. Age at time of presentation and pH level were predictors of neuroimaging and functional outcomes. CONCLUSIONS DKA at type 1 diabetes diagnosis results in morphologic and functional brain changes. These changes are associated with adverse neurocognitive outcomes in the medium term.