Background: The study of muscle metabolism by near-infrared spectroscopy (NIRS) has been poorly implemented in multiple sclerosis (MS). Aims of the study were to compare resting muscle oxygen consumption (rmVO2) at gastrocnemius in MS patients and in age-matched healthy controls (HC) measured using NIRS, and to evaluate its possible relationship with patients' mobility.Methods: Twenty-eight consecutively enrolled MS patients (male, n = 16; age = 42.7 ± 14.0 y, Relapsing-Remitting, n = 19; Primary-Progressive, n = 9) and 22 HC (male, n = 13; age = 36.0 ± 8.2 y) were studied during rest applying the NIRS probes at gastrocnemius, producing a venous occlusion at the thigh using a cuff, and analyzing the slope of the total hemoglobin to calculate rmVO2. Mobility was assessed by a 6-Minute Walking Test and 6-Minute Walking Distance (6MWD) was recorded.Results: rmVO2 was higher in MS compared to HC (0.059 ± 0.038 vs 0.039 ± 0.016 mlO2/min/100 g, P < 0.003), not different in clinical subtypes, not correlated to patients' characteristics (age, disease duration, Expanded Disability Status Scale, resting heart rate, skinfold thickness), and significantly higher in patients with lower walking ability (6MWD < 450 m, n = 12) compared to those at better performance (respectively, 0.072 ± 0.043 vs 0.049 ± 0.032 mlO2/min/100 g, P = 0.03).Conclusion: rmVO2 values, significantly higher in MS patients compared to HC, and in low versus high performing patients, might represent a marker of peripheral adaptations occurred to sustain mobility, as observed in other chronic diseases. © 2013 Malagoni et al.; licensee BioMed Central Ltd.