This study examined overall and specific symptoms as cross-sectional correlates of physical activity in persons with relapsing-remitting multiple sclerosis (RRMS). We expected that overall symptoms would be inversely associated with physical activity, and that the association would be accounted for by fatigue, depression, and pain. The sample included 269 individuals with a definite diagnosis of RRMS who completed a battery of questionnaires and then wore an accelerometer for 7 days. Data were analyzed using covariance modeling in Mplus. The primary model (chi square = 13.89, df = 10, p = 0.18, SRMR = 0.03, comparative fit index = 0.99) demonstrated that the path between overall symptoms and physical activity was indirect by way of fatigue (indirect path coefficient = -0.15) and depression (indirect path coefficient = -0.10). Such findings provide support for an indirect association between overall symptoms and physical activity by way of fatigue and depression in RRMS.