The present study examined the relationships among parameters (i.e., volume and pattern) of physical activity and sedentary behavior with the presence and severity of restless legs syndrome(RLS) in adults with multiple sclerosis(MS). Participants with MS (N = 253) wore an accelerometer for a 7-day period and completed the Cambridge-Hopkins Restless Legs Syndrome Questionnaire, the International Restless Legs Syndrome Study Group Scale (IRLS), and the Patient Determined Disease Steps scale. Sixty-six (26%) persons with MS had RLS (MS + RLS). There were no differences between the MS + RLS and MS group for parameters of physical activity or sedentary behavior. Among participants with IRLS scores in the mild range (n = 26), more time spent in light physical activity (r = 0.39), fewer sedentary bouts per day (r = 0.55), less time in sedentary bouts per day (r = 0.51), and fewer breaks in sedentary time per day (r = 0.57) were associated with lower RLS severity. This study represents the first step toward recognizing a relationship between physical activity, patterns of sedentary behavior, and RLS severity in MS and these results suggest that light physical activity and the pattern of sedentary behavior may be important targets for prospective behavioral interventions that target the management of RLS in persons with MS who have mild RLS severity.