Objective: To assess and compare the frequencies of personal and family history of autoimmune diseases (AID), autoinflammatory disorders (ID), and allergies in a population of patients, adults and children, with narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH), 3 central hypersomnia disorders, and healthy controls. Methods: Personal and family history of AID, ID, and allergies were assessed by questionnaire and medical interview in a large cohort of 450 consecutive adult patients (206 NT1, 106 NT2, 138 IH) and 95 pediatric patients (80 NT1) diagnosed according to the third International Classification of Sleep Disorders criteria in national reference centers for narcolepsy in France and 751 controls (700 adults, 51 children) from the general population. Results: Ten adults with NT1 (4.9%) had a comorbid AID vs 3.4% of adult controls, without between-group differences in adjusted models. AID frequency did not differ between children with NT1 and controls. Conversely, compared with controls, AID frequency was higher in adults with NT2 (p 5 0.002), whereas ID (p 5 0.0002) and allergy (p 5 0.003) frequencies were higher in adults with IH. A positive family history of AID was found in the NT1 group and of ID in the IH group. Conclusions: NT1 is not associated with increased risk of comorbid immune disorders, in favor of a potentially unique pathophysiology. Conversely, compared with controls, the frequency of auto-immune diseases was higher in adults with NT2, whereas allergies and autoinflammatory disorders were more common in adults with IH, suggesting an immune dysregulation mechanism in these conditions. Neurology ® 2017;88:93–100 GLOSSARY AID 5 autoimmune disease; BDI 5 Beck Depression Inventory; BMI 5 body mass index; CI 5 confidence interval; EDS 5 excessive daytime sleepiness; HLA 5 human leukocyte antigen; ID 5 autoinflammatory disorders; IH 5 idiopathic hyper-somnia; MSLT 5 Multiple Sleep Latency Test; NT1 5 narcolepsy type 1; NT2 5 narcolepsy type 2; OR 5 odds ratio; SOREMP 5 sleep-onset REM period. Narcolepsy type 1 (NT1), formerly called narcolepsy with cataplexy, is a rare disease caused by the selective loss of hypothalamic hypocretin/orexin neurons. 1–3 The mechanism of the destruction of these neurons remains unclear; however, an autoimmune process is the most probable hypothesis. Epidemiologic and clinical findings (i.e., rare family cases, frequent discordance in monozygotic twins, young and bimodal age at onset, 1,4 and the association with the H1N1 influenza pandemic and its vaccine or with streptococcal infections 5–8) are in favor of this hypothesis. Moreover, a tight genetic association with specific human leukocyte antigen (HLA) class II (DQB1*06:02) 9 and more recently HLA class I haplotypes was highlighted 10,11 as well as with other immune gene variants, such as the purinergic receptor subtype P2RY11 12 and T-cell receptor a locus. 13 Several cytokines with proinflammatory properties, especially interferon-g, and antibodies against different brain antigens have been identified in NT1,