IntroductionPhysiological fitness, encompassing cardiorespiratory fitness (CRF) and body composition, are important markers of overall health, functional capacity, and quality of life in general and clinical populations. Characterizing fitness is important for the development of tailored interventions and strategies to optimize well-being across the spectrum of disability in multiple sclerosis (MS). While existing research has explored fitness in people with mild-to-moderate disability, there is a scarcity of data in people with advanced MS (Expanded Disability Severity Scale, EDSS≥7.0). ObjectiveTo characterize CRF and body composition and their associations with fatigue, quality of life, and function in individuals with advanced MS. MethodsParticipants (n=18, mean age=60.7 years-old, median EDSS=7.5) underwent a cardiopulmonary exercise test and dual-energy X-ray absorptiometry scanning. Main outcomes included peak volume of oxygen uptake (V̇O2peak) and whole and regional body fat, lean mass, bone mineral content, and bone density. Symptoms of fatigue (Modified Fatigue Impact Scale, MFIS), quality of life (29-item MS Impact Scale, MSIS-29), and daily function (Late-Life Function and Disability Instrument, LLFDI) were collected. ResultsParticipants exhibited notably low CRF levels (V̇O2peak=9.8 mL/min/kg) and poor body composition (lower lean mass, bone mineral content and density) compared to previous studies in the general population and in individuals with MS with lower disability. V̇O2peak was most consistently associated with function in daily life (LLFDI scores, rs≥0.637, p≤0.004). ConclusionThese findings reinforce the potential importance of physiological fitness to preserve function in people with advanced MS.