We compared the explanatory power of two symptom clusters that consisted of either three or five symptoms as correlates of physical activity in individuals with relapsing-remitting multiple sclerosis (RRMS; N = 218). The data were primarily analyzed using covariance modeling in Mplus 3.0. A symptom cluster of fatigue, depression, and pain had a moderate, negative relationship with physical activity, and this relationship was comparable in magnitude with a symptom cluster of fatigue, depression, pain, perceived cognitive dysfunction, and poor sleep quality. The relationships were attenuated after controlling for exercise history and neurological impairment. Such findings further support the consideration of a narrowly defined cluster of three symptoms as an independent correlate of physical activity in persons with RRMS.