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Background: Multiple sclerosis (MS) is a progressive and neurodegenerative disease of the central nervous system. Its symptoms vary greatly, which makes its diagnosis complex, expensive, and time-consuming. One of its most prevalent symptoms is muscle fatigue. It occurs in about 92% of patients with MS (PwMS) and is defined as a decrease in maximal strength or energy production in response to contractile activity. This article aims to compare the behavior of a healthy control (HC) with that of a patient with MS before and after muscle fatigue., Methods: For this purpose, a static baropodometric test and a dynamic electromyographic analysis are performed to calculate the area of the stabilometric ellipse, the remitting MS (RMS) value, and the sample entropy (SampEn) of the signals, as a proof of concept to explore the feasibility of this test in the muscle fatigue quantitative analysis; in addition, the statistical analysis was realized to verify the results., Results: According to the results, the ellipse area increased in the presence of muscle fatigue, indicating a decrease in postural stability. Likewise, the RMS value increased in the MS patient and decreased in the HC subject and the opposite behavior in the SampEn was observed in the presence of muscle fatigue., Conclusion: Thus, this study demonstrates that SampEn is a viable parameter to estimate muscle fatigue in PwMS and other neuromuscular diseases., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Medical Signals & Sensors.)