OBJECTIVE This study assessed whether a single diabetic ketoacidosis (DKA) episode is associated with cognitive declines in children with newly diagnosed type 1 diabetes and whether the same is true in children who had previously been diagnosed after accounting for variations in glycemic control and other relevant factors. RESEARCH DESIGN AND METHODS We prospectively enrolled 758 children, 6–18 years old, who presented with DKA in a randomized multisite clinical trial evaluating intravenous fluid protocols for DKA treatment. DKA was moderate/severe in 430 children and mild in 328 children. A total of 392 children with DKA had new onset of type 1 diabetes, and the rest were previously diagnosed. Neurocognitive assessment occurred 2–6 months after the DKA episode. A comparison group of 376 children with type 1 diabetes, but no DKA exposure, was also enrolled. RESULTS Among all patients, moderate/severe DKA was associated with lower intelligence quotient (IQ) (b 5 20.12, P < 0.001), item-color recall (b 5 20.08, P 5 0.010), and forward digit span (b 5 20.06, P 5 0.04). Among newly diagnosed patients, moderate/severe DKA was associated with lower item-color recall (b 520.08, P 5 0.04). Among previously diagnosed patients, repeated DKA exposure and higher HbA1c were independently associated with lower IQ (b 5 20.10 and b 5 20.09, respectively, P < 0.01) and higher HbA1c was associated with lower item-color recall (b 5 20.10, P 5 0.007) after hypoglycemia, diabetes duration, and socioeconomic status were accounted for. CONCLUSIONS A single DKA episode is associated with subtle memory declines soon after type 1 diabetes diagnosis. Sizable IQ declines are detectable in children with known diabetes, suggesting that DKA effects may be exacerbated in children with chronic exposure to hyperglycemia.