Comfortable walking speed and energy cost of walking are physiological markers of metabolic activity during gait. People with multiple sclerosis are characterized by altered gait biomechanics and energetics, related to the degree of disability and spasticity, which lead to an increased energy cost of walking. Several studies concerning the energy cost of walking in multiple sclerosis have been published. Nevertheless, differences in protocols and characteristics of the sample have led to different outcomes. The aim of the present meta-analysis is to summarize results from studies with specific inclusion characteristics, and to present data about the comfortable walking speed and the energy cost of walking at that speed. Moreover, a detailed discussion of the potential mechanisms involved in the altered metabolic activity during exercise was included. A total of 19 studies were considered, 12 of which were also part of the quantitative analysis. Despite the strict selection process, high between-group heterogeneity was found for both outcomes. Nevertheless, the overall results suggest a pooled mean comfortable walking speed of 1.12 m/s (95% CI 1.05-1.18) and energy cost of 0.19 mLO2/kg/m (95% CI 0.17-0.21). These findings support the results of previous studies suggesting that energy cost of walking may be increased by 2-3 times compared to healthy controls (HC), and encourage the use of this marker in association with other parameters of the disease.