Despite frequent muscle strength or muscle oxidative capacity (based on exercise-onset oxygen uptake [VO2] kinetics) assessments in patients with multiple sclerosis, the impact of time of day on these parameters is often not taken into account. Based on observations in healthy subjects, it remains to be studied whether muscle strength, and/or exercise-onset VO2 kinetics, varies between the morning and the afternoon in patients with multiple sclerosis. In this prospective observational pilot study, walking capacity, exercise-onset VO2 kinetics, isometric knee extension/flexion strength (dynamometry), and self-reported fatigue were measured in 11 patients with multiple sclerosis (age, 51.8 ± 9.3 yrs; body mass index, 24.7 ± 5.1 kg/m2; Expanded Disability Status Scale, 3.5 ± 1.4; 3 men) in the morning and 5 hrs later (afternoon). In the afternoon, self-reported fatigue (1.9 ± 0.9 cm) and muscle strength (knee extension peak torque at 45 degrees, 84 ± 26 Nm) were significantly different (P < 0.05), than in the morning (self-reported fatigue, 1.2 ± 0.9 cm; knee extension peak torque at 45 degrees, 93 ± 32 Nm), but walking capacity and exercise-onset VO2 kinetics were similar at these two time points (P > 0.05). Consistent with observations in healthy subjects, muscle strength varies between the morning and the afternoon in patients with multiple sclerosis, under the conditions of the present study. These findings suggest that muscle strength assessments should be conducted at similar or nearly similar times of the day to minimize diurnal variation in these measures and hence insure correct interpretation.