BACKGROUND: Spinal cord volume loss is associated with clinical disability in multiple sclerosis (MS). Aerobic capacity may mitigate the impact of central nervous system (CNS) damage accumulation, exerting beneficial effects on MS-related disability. OBJECTIVES: We investigated whether aerobic capacity could moderate the association between spinal cord atrophy and clinical disability in MS. METHODS: In this cross-sectional analysis, expanded disability status scale (EDSS), peak of oxygen consumption (VO RESULTS: The relationship between nMUCCA and EDSS was moderated by aerobic capacity, with a significant nMUCCA × aerobic capacity interaction (β = -0.099, 95% bootstrapped confidence interval [CI] = [-0.172
-0.014], CONCLUSIONS: In MS patients with mild disability, higher aerobic capacity can potentially mitigate the negative impact of spinal cord damage on clinical disability.