Introduction. The Expanded Disability Status Scale (EDSS) is the most widely used disability measure in multiple sclerosis (MS). The effect of fatigability on EDSS components has been underreported to date. Objective We investigated daytime variability in EDSS score and EDSS components - functional scores (FS) and walking distance (WD) up to 500 m, in MS patients who underwent a standardized fatiguing exercise. Methods. Twenty-four patients with relapsing-remitting MS (n = 7), secondary-progressive MS (n = 8) and primary-progressive MS (n = 9) were included. Exclusion criteria were as follows: current MS relapse, infection/fever/flu-like symptoms, conditions prohibiting safe exercise testing, current medication affecting fatigue. One trained examiner performed baseline (BL) and follow-up (FU) assessments (FU1 after a standardized fatiguing exercise, FU2 after rest) over a single day. EDSS score change of ?1 point if BL EDSS score was <5.5 or of ?0.5 point if BL EDSS score was ?5.5 were considered clinically meaningful. Results. In progressive MS subtypes, WD decreased at FU1, but recovered at FU2, more so in secondaryprogressive MS subgroup with the highest BL EDSS score. Although BL EDSS scores (median, 5.0; range 4.0-6.5) and FS remained relatively stable over repeated assessments in the total group, a clinically meaningful transitory post-exercise EDSS score increase was observed in three patients with progressive MS. Conclusion. WD seems to be more influenced by fatigability than the total EDSS score, more so in patients with progressive MS and higher disability. WD should be assessed after rest and this strategy should be implemented into protocols of clinical trials recruiting patients with progressive MS phenotypes.