The present study examined the relationship between the worsening of symptoms across a 3-5-year period of time and self-reported physical activity in a sample of 51 individuals with multiple sclerosis (MS). Of the 51 participants, 35 reported a worsening of symptoms over the 3-5-year period of time. The worsening of symptoms was associated with significantly and moderately lower levels of self-reported physical activity independent of depression and EDSS scores and MS-disease course (P=0.04). This study provides novel evidence that a worsening of symptoms is associated with lower levels of physical activity in individuals with MS.