The coronavirus disease 2019 pandemic and postpandemic era have significantly impacted the physical, mental, and social health (global health) of people with multiple sclerosis (MS). Extensive evidence highlights the positive relationships among global health, employment, and subjective well-being. For rehabilitation psychologists and health professionals serving individuals with MS, it is crucial to incorporate a global health measure into their assessment toolkit. The Patient-Reported Outcomes Measurement Information System Global Health (PROMIS©GH) Scale is widely used and validated for diverse patient populations worldwide. However, there is no study that validates the PROMIS©GH for people with MS. We conducted an exploratory factor analysis with a sample of U.S. adults with MS (N = 495) to examine the measurement structure of the PROMIS©GH. Exploratory factor analysis results indicated a two-factor measurement structure (physical health and mental-social health) that accounted for 67.80% of the total variance. All items loaded highly onto their respective factors (ranging from 0.59 to 0.93). The Cronbach's α of the two subscales was .85 and .86, which is high for very brief measures. The two factors were significantly and positively associated with employment, subjective well-being, resilience, core self-evaluations, and social support, and negatively associated with stress and depression in the theoretically expected directions, supporting its construct validity. The findings of this study indicated that PROMIS©GH is a psychometrically sound global health measure for people with MS and should be included as a health assessment tool for rehabilitation psychologists and health professionals who provide services to people with MS. (PsycInfo Database Record (c) 2024 APA, all rights reserved).