The Brief International Classification of Functioning, Disability and Health (ICF) Core Set for MS was developed to capture functioning in people with multiple sclerosis (pwMS). This study examined whether categories in the Brief ICF Core Set for MS best capture different levels of functioning in pwMS. We used data of a multicenter cross-sectional study collected from 205 pwMS using the ICF categories of the MS-specific WHO ICF Checklist and the individual rating of functioning. ICF categories to be entered in an initial regression model were selected following a systematic procedure in accordance with the ICF structure. Based on the initial regression model using stepwise Ordinary Least-Squares regression analyses, additional models were designed by substituting the ICF categories in final model. The selected set of categories was compared with the Brief ICF Core Set for MS. Eleven ICF categories were identified that best differentiate among different levels of functioning. Four were part of the Brief ICF Core Set. ICF categories identified in this study may be used as outcome measures in further study, parameters to monitor functioning along the continuum of health care and lifespan, and to define different subgroups of pwMS.