Background: There has been limited research on upper limb dysfunction in people with multiple sclerosis (PwMS). Objective: The objective of this paper is to study unilateral and bilateral upper limb dysfunction at different International Classification of Functioning (ICF) levels according to overall disability in PwMS. Methods: A total of 105 PwMS (16 with EDSS<4 (mild); 17 with EDSS 4–5.5 (moderate); 37 with EDSS 6–6.5 (severe); 35 with EDSS>6.5 (severe non-ambulant)) were recruited from two rehabilitation centers and assessed in a cross-sectional study. Results: The whole sample showed a diminished sensory function (median (first/third interquartile)) score of 3 (2/3) on the Monofilament Test and a reduced strength 91 (76/100) points on the Motricity Index (Body-Function level). Sensory dysfunction did not increase with higher EDSS while strength decreased from 100 (86/100) in the mild subgroups to 91 (80/100) points in the severe subgroup. All showed diminished dexterity, scoring 0.28 peg/s (0.17/0.35) on the Nine-Hole Peg Test (NHPT) (activity level). Score was better for the mild (0.38 (0.35/0.46)) peg/s compared to the severe subgroup (0.28 (0.17/0.35)). Sixty-eight percent, 44% and 75% of PwMS showed bilateral disorders in sensation, strength and dexterity, respectively. The Community Integration Questionnaire (participation level) showed a 35% reduction in home activities, even among PwMS with EDSS<4. Conclusion: This study showed uni-/bilateral upper limb abnormalities at all ICF levels increasing with the overall disability.