Purpose: To describe symptom clusters based on severity of co-occurring symptoms among adults with multiple sclerosis (MS) by age groups and to further examine symptom clusters as a correlate of quality of life (QOL) by age groups., Methods: This cross-sectional study enrolled persons with MS between 20 and 79 years of age who completed measures of fatigue, depression, anxiety, sleep quality, and QOL using the 36-Item Short Form Health Survey. Bivariate correlation and partial correlation analyses examined associations among symptoms, QOL, and MS characteristics. K-means cluster analyses determined symptom clusters among the full sample and pre-determined age groups (i.e., 20-39, 40-59, and 60-79). One-way ANOVAs examined differences in QOL among clusters for the overall sample and by age groups., Results: Among the overall sample of 205 participants, symptoms were significantly correlated with QOL and three distinct clusters were identified and differentiated by the magnitude of symptom experience (i.e., mild, moderate, and severe). Results were consistent among young and middle-aged adults; however, among older adults two severe sleep problem clusters were identified that were distinguished by moderate versus severe fatigue, depression, and anxiety. ANOVAs among the overall sample indicated that the three symptom clusters varied significantly for both physical component scores, F(2, 202) = 12.03, p < .001, η 2 = .10, and mental component scores, F(2, 202) = 137.92, p < .001, η 2 = .58; severe symptom cluster was associated with worse QOL. Patterns in the age subgroup ANOVAs were consistent., Conclusions: Given the strong association between severity of symptom clusters and QOL, approaches for targeting co-occurring symptoms are critically needed.