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Objective: To examine the association among body composition, defined as the percentage of body fat mass (BF) and lean mass (LM), bone mineral content (BMC) and bone mineral density (BMD) in the human body and the presentation of symptoms (i.e., fatigue, pain, depression, anxiety, and poor sleep quality) in persons with multiple sclerosis (MS). Design: The present study is a secondary analysis of baseline data from a physical activity intervention for persons with MS. The research question was informed by the theory of unpleasant symptoms, namely an examination of the relationship between body composition (i.e., physiologic antecedent) and symptoms in this sample of 77 participants with MS. The association between body composition and symptoms was examined using partial correlation analyses controlling for age, sex, and disability status. Results: Participants were 49 ± 9 years of age on average and diagnosed with MS for an average of 12 ± 8 years. Most participants identified as female (74%), reported having a relapsing−remitting disease course (78%), and moderate MS-related disability based on a median (interquartile range) Patient Determined Disease Steps score of 3.0 (3.0). Partial correlation analyses indicate there were no significant correlations observed among body composition (%BF, %LM, BMC, and BMD) and any symptoms (fatigue, pain, depression, anxiety, and sleep quality). Conclusion: Additional research that examines other physiologic factors as well as psychological and situational factors based on the theory of unpleasant symptoms that might account for symptoms in persons with MS is necessary. This will inform behavioral interventions and rehabilitation programs that target theory-based factors such as correlates of symptoms in MS.