Phenobarbital is useful in controlling simple and complex partial seizures and generalized tonic-clonic seizures in children. It has traditionally been considered the first choice to treat neonatal seizures (seizures in newborn infants). Most studies have found that phenobarbital controls these seizures in about one-third of the infants.

Phenobarbital also has been widely used to prevent recurrent febrile seizures (seizures accompanying a high fever in infants or young children). Because 2 days or more may be required to achieve a high enough level of medication in the blood to control seizures, giving phenobarbital after a fever begins will not be effective. Instead, it must be given daily. One study found that 4% of children treated with an adequate daily dose had a repetition of these seizures, compared to 20% of untreated children. Because febrile seizures usually cause no lasting harm, however, most children should not be given medication for them.

Some doctors hesitate to prescribe phenobarbital for children because it has a reputation for causing behavioral or learning problems in children. Some studies have found that phenobarbital worsens pre-existing hyperactivity and aggressive tendencies. Many physicians believe that phenobarbital sedates children, with a greater effect at higher doses. A number of studies have not found any sedation, however, perhaps because some children become extra alert and their scores cancel out those of sedated children. Nevertheless, the problems with phenobarbital should not be overestimated.

Nevertheless, some studies have found subtle learning impairments in children who are given phenobarbital over a long period, so other seizure medicines may be preferred as a first choice for long-term use in children.

Side effects are much more likely to be troublesome if high doses are given or if too high a dose is given to start. It may be necessary to increase the dosage very slowly over several months. Dosages for children are based on weight: the usual dose for children is 1 to 6 mg per kilogram (2.2 pounds) of body weight per day.