OBJECTIVE: A network meta-analysis (NMA) of current evidence was conducted to determine if physical exercise has a positive influence on multiple sclerosis (MS) fatigue and type of exercise with the largest effect on fatigue also according to disease severity. DATA SOURCES: Medline, Embase, SPORTDiscus, PEDro, Cochrane Library and Web of Science. The search strategy combined relevant terms related to: (a) multiple sclerosis; (b) clinical trials; (c) exercise; and (d) fatigue, from inception to February 2021. STUDY SELECTION: Randomized controlled trials concerning the effectiveness of different types of exercise on total and physical fatigue in people with MS were included. DATA EXTRACTION: The data were extracted into predesigned data extraction tables. Risk of bias was evaluated with the Cochrane risk of bias tool (RoB 2.0) and to evaluate the quality of the evidence, the Grading of Recommendations, Assessment, Development and Evaluation tool was used. DATA SYNTHESIS: A total of 58 studies were examined. Data were pooled using a random effects model. A ranking of seven and eight different exercise interventions for physical and total fatigue scores, respectively, was achieved. The highest effects for pairwise comparisons were for combined exercise and resistance training versus control (ranging between -0.74 and -1.24). In the NMA, combined exercise (-1.51; 95% CI -2.01 to -1.01) and resistance training (-1.15; 95% CI -1.81 to -0.49) compared to the control group achieved the highest effects for physical and total fatigue, respectively. CONCLUSION: Exercise should be considered an effective fatigue management strategy. Among the different exercise modalities, combined exercise is the most effective exercise modality for improving both, physical and total fatigue. Resistance training is also an effective exercise for total fatigue among people diagnosed with MS.

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