The role of laboratory tests in the treatment of patients with unprovoked seizures in the emergency department (ED) is unclear. To better determine the diagnostic value of routine serum chemistries (glucose, electrolytes) in these patients, and to identify risk factors predicting abnormality, 107 children who presented to the ED with unprovoked seizures were evaluated prospectively. Serum electrolytes and glucose were determined in 54 patients. The incidence of abnormal serum biochemical values was 14.8%; it was higher in patients with a first seizure, younger age, gastrointestinal symptoms, or change in mental status. These data indicate that serum glucose and/or electrolyte abnormalities are rare in patients evaluated in the ED for unprovoked seizures. Based on these findings and those reported in previous studies, performance of these tests is recommended in children younger than 2 years old, presenting with a first seizure, or when accompanied by gastrointestinal or diffuse neurologic symptoms.