This study was performed to evaluate the actions of baclofen and sodium oxybate, two medications with gamma-aminobutyric acid type B (GABA(B)) receptor agonist properties, on symptoms of narcolepsy in drug-naïve teenagers. Twenty-six narcoleptic teenagers with recent onset of narcolepsy-cataplexy syndrome who were human leukocyte antigen DQB1 0602 positive were matched for age and sex and received either baclofen or sodium oxybate. If deemed necessary to combat excessive daytime sleepiness, the alerting agent modafinil was also prescribed. Clinical evaluation was performed weekly, and visual analog sleepiness score and cataplexy logs were collected weekly. The Epworth Sleepiness Scale or the Pediatric Daytime Sleepiness Scale, polysomnography, and the Multiple Sleep Latency Test were recorded at baseline and after 3 months of drug intake. The dose of baclofen demonstrating an effect on nocturnal sleep without negative side effects was determined and maintained. Both drugs increased total sleep time and delta waves during sleep, but only sodium oxybate had an effect on daytime sleepiness and cataplexy at 3 months. Improvement of total nocturnal sleep time had no beneficial effect on daytime sleepiness. The mechanism by which sodium oxybate improves cataplexy and sleepiness is inferred to be due to properties beyond direct GABA(B) agonist action.