Objective Fatigue experienced by persons with multiple sclerosis (pwMS) is multidimensional, consisting of different components, such as perceived, physical and cognitive fatigue and performance fatigability. Actually, there is no gold standard to assess performance fatigability in pwMS; therefore, we aimed at determining if during a fatiguing task, average rectified value (ARV), mean frequency of the power spectrum (MNF), muscle fiber conduction velocity (CV) and fractal dimension (FD) of the sEMG may be used as indirect indices of performance fatigability. Moreover, we analyzed if a 3-week rehabilitation program impacts on performance fatigability in pwMS and whether a relationship between sEMG parameters and trait levels of perceived fatigability, before and after rehabilitation does exist. Approach Twenty-one pwMS performed a 20% maximal voluntary contraction (MVC) of 1 min, and afterwards a 60% MVC held until exhaustion. sEMG signals were detected from biceps brachii, vastus medialis and lateralis. Performance fatigability was determined at entry (t0) and discharge (t1) to rehabilitation. Perceived fatigability was measured at t0 and t2, one month after rehabilitation. Main results ARV, MNF, CV and FD rates of change showed at t0 and t1 significant changes (p<0.05) during the high level contraction in the biceps brachii, whereas rather limited in the vastii muscles. Moreover, rehabilitation did not induce any reductions nor in perceived neither in performance fatigability. No significant correlations between ARV, MNF, CV and FD rates of change during the 60% MVC and perceived fatigability, at t0 and t2, was found. Significance Our findings suggest that the sEMG parameters are useful to indirectly assess performance fatigability in pwMS during sub-maximal fatiguing contractions, particularly in the biceps brachii.