Neuron-specific enolase, a marker for neuronal injury, is elevated following seizures in adults, but relatively few data exist on postictal neuron-specific enolase levels in children. This study measured cerebrospinal fluid (CSF) neuron-specific enolase levels after seizures in 49 consecutive pediatric patients and investigated the role of seizure type, duration, and etiology in influencing neuron-specific enolase. Overall, there was no significant difference in neuron-specific enolase levels between patients with seizures and a control group. However, 4 of the 49 seizure patients (8%) had neuron-specific enolase levels clearly above the normal range. Seizure patients with symptomatic etiologies had significantly increased neuron-specific enolase compared to cryptogenic/idiopathic or febrile seizures. The four individual patients with elevated cerebrospinal fluid neuron-specific enolase all had identified metabolic or genetic etiologies and presented with medically refractory status epilepticus. No individuals with cryptogenic/idiopathic or febrile seizures had abnormal neuron-specific enolase. There was no significant effect of seizure duration or type on cerebrospinal fluid neuron-specific enolase. In contrast to adults, acute seizure-induced neuronal injury in children as detected by neuron-specific enolase is rare and may occur primarily with severe symptomatic etiologies. Children with cryptogenic, idiopathic, or febrile seizures, including status epilepticus, are at relatively low risk for neuronal damage following seizures.