Abstract Introduction The pathogenesis of multiple sclerosis (MS)-related fatigue is multi-factorial, including neurogenic, inflammatory, endocrine, metabolic, mood, as well as sleep disorder-related mechanisms. The confounding effect of sleep disorders on the association between fatigue and neurodegenerative changes in the brain has not been investigated. Our objectives were to assess the prevalence of sleep apnea and periodic limb movements in the framework of a prospective study which investigates the neurogenic causation of treatment-resistant fatigue in MS. Methods MS patients enrolled in a National MS Society-funded prospective study (grant identifier RG-1501-03141) underwent a one-night at-home sleep test (HST) using a NOX T3 portable monitor. HST recordings were scored by a registered polysomnographic technologist. Respiratory Event (REI) and Periodic Limb Movement (PLMI) Indices were calculated for each patient. Results Out of 36 patients, 7 (20%) had mild (REI=5-14), 1 (3%) had moderate (REI=15-29), and 1 (3%) had severe sleep-disordered breathing (REI≥30). Fourteen (42%) of the patients had mild (PLMI=5-24), 4 (11%) had moderate (PLMI=25-49), and 7 (19%) had severe periodic limb movements (PLMI≥50). Overall, 81% of the patients had at least mild sleep-disordered breathing and/or periodic limb movements. Conclusion Sleep abnormalities (i.e., sleep apnea and periodic limb movements) are highly prevalent in patients with MS. We plan to compare the MRI exams of subgroups of MS patients with fatigue, to test the hypothesis that fronto-striatal circuitry is more affected by lesions in patients without sleep apnea compared to those with sleep apnea. Support This investigation was supported by a grant from the National Multiple Sclerosis Society (grant identifier RG-1501-03141). The home sleep test equipment was provided by a DURIP grant from the Office of Naval Research (grant N00014-15-1-2917).