BackgroundPerceived fatigue and fatigability are constructs of multiple sclerosis (MS)-related fatigue. Sleep disturbances lead to poor sleep quality, which has been found to be associated with perceived fatigue in people with MS (PwMS). However, the relationship between fatigability and sleep quality is unknown.ObjectiveTo explore the relationship between physical and cognitive fatigability with self-reported and objective measures of sleep quality in PwMS.MethodsFifty-one ambulatory PwMS participated in the study. Physical fatigability was measured by percent-change in meters walked on the six-minute walk test (6MWT) and in force exerted on a repeated maximal hand grip test. Cognitive fatigability was measured using response speed variability on the continuous performance test. Self-report sleep quality was measured using the Pittsburgh Sleep Quality Index, and objective sleep quality was measured using 1 week of actigraphy.ResultsComponents of the Pittsburgh Sleep Quality Index and several actigraph parameters were significantly associated with physical fatigability and cognitive fatigability. However, controlling for depression eliminated the association between the sleep outcomes and cognitive fatigability and attenuated the association between the sleep outcomes and physical fatigability.ConclusionPoor sleep quality is related to fatigability in MS but depression appears to mediate these relationships.