Narcolepsy is a sleep disorder caused by defective hypocretin (orexin) neurotransmission. It is thought to result from an autoimmune destruction of hypocretin producing neurons. Recently, low hypocretin levels were found in patients with Guillain-Barré syndrome, a post-infectious immune-mediated disorder in which a variety of circulating antibodies against neuronal gangliosides are found. We therefore considered gangliosides to be candidate antigens in narcolepsy as well, and screened for the presence of a panel of serum anti-ganglioside antibodies in a group of 28 well-characterized narcoleptic patients. We did not find a correlation between increased titers of anti-ganglioside antibodies and hypocretin-deficient narcolepsy. This study does not support the hypothesis that an autoimmune response is involved in narcolepsy. However, as an autoimmune attack may be selective and/or transient, future studies are needed to ultimately refute or confirm the autoimmune hypothesis.