PURPOSE: Evaluation of skeletal muscle oxidative capacity in people with multiple sclerosis (MS) using near-infrared spectroscopy (NIRS) and its relationship with measures of walking disability. METHODS: Muscle oxidative capacity was measured in an MS and control (CON) group with near- infrared spectroscopy (NIRS) during repeated arterial occlusions to assess rate of recovery of muscle oxygen consumption in both gastrocnemius muscles after exercise. Walking disability was assessed by a timed 25-ft walk and fatigue questionnaires. RESULTS: Oxidative capacity on average was lower in the MS group compared to CON group (1.13 ± 0.29 vs. 1.68 ± 0.37 min-1, p < 0.05). 25-ft walk time was slower in patients with MS compared to CON group (3.72 ± 0.40 vs. 8.50 ± 6.23 sec, p < 0.05). The participants with MS who used an assistive device during the 25-ft walk test walked significantly slower than those who used no assistive device (p < 0.01). Significant correlations were found between oxidative capacity in the self-reported most-affected leg and percent difference between oxidative capacity of the self-reported most-affected and least-affected legs and Modified Fatigue Impact Scale questionnaire total and physical score. CONCLUSION: NIRS measurements of oxidative capacity suggest a 40% deficit in people with MS compared to healthy controls, consistent with previous studies using 31P MRS. Preliminary evidence suggest the magnitude of bilateral oxidative capacity deficits may be a bimodal indicator of walking dysfunction.