OBJECTIVES: Reports from clinical trials suggest that physical activity (PA) can be beneficial for multiple sclerosis (MS) patients. However, participation in PA was found to be low in MS patients with substantial physical disability. We assessed levels of PA and their interaction with depression and health related quality of life (HRQoL) in early-stage MS patients. METHODS: The BEGIN study (Betaferon® treatment and Exercise data Gathering IN early MS) is an international prospective observational study of early-stage MS patients, including clinically isolated syndrome suggestive of MS, treated with Betaferon®. PA levels were assessed by the International Physical Activity Questionnaire (IPAQ) and a pedometer, and depression using the Center for Epidemiological Studies Depression Scale (CES-D), and HRQoL with the EuroQoL 5 dimension (EQ-5D) utility scale and Visual Analogue Scale (VAS) score. RESULTS: PA data were collected from 609 patients (68.0% women) in 16 countries in Europe, Asia, Australia and Latin America. Mean age was 36.3 years (SD=9.9). The median MET-minutes/week derived from IPAQ at baseline was 3349 (SD=3616), with 25.2%, 32.5% and 42.6% of patients categorized as low, moderate and high PA level, respectively. The median steps per day were 6,728 (IQR=4,942). A negative Spearman’s rank correlation was found between the steps per day and depressive symptoms (p<0.01).Mean depression scores decreased monotonically in higher IPAQ categories. EQ-5D utility and VAS scores were on average 0.7 (SD=0.2) and 71.7 (SD=19.5), respectively. The steps per day showed to be positively correlated with both VAS (p=0.01) and utility (p<0.01) outcomes. CONCLUSIONS: PA in early-stage MS patients was found to be positively associated with HRQoL. Adding the results of the longitudinal data after two years of follow-up may lead to further insights regarding the role of  PA in early-stage MS patients and its relation to HRQoL.