Background: Fatigue is among the most frequent and disabling symptoms in RMS patients. Objectives: To measure multiple sclerosis (MS) fatigue and its impact on daily life in a real-world population using a survey including the relapsing MS (RMS)-specific Fatigue Symptoms and Impacts Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS). Methods: This is an ongoing noninterventional prospective study of RMS patients recruited across the USA via an online survey. Participants completed questionnaires including disease history, disease status, sleep, social and emotional functioning, and the FSIQ-RMS, administered daily for 7 days. The FSIQ-RMS measures self-reported fatigue, and scores range from 0-100 (higher score = greater severity). Results: A total of 300 RMS participants completed the 7-day assessment: mean age: 43.0 yrs; 88% women; mean diagnosis age: 32 yrs. Fatigue was reported as the symptom with the greatest impact on daily functioning. Fatigue was rated as severe, with a mean score of 57.3 for the FSIQ-RMS symptom domain; 3 impact sub-domain scores were 42.3, 43.4 and 50.1 (physical, cognitive/emotional, and coping). Most participants (78%) were outside the window of a self-reported relapse, and reported less severe fatigue than those in relapse: mean fatigue symptom domain score of 54.6±17.8 vs. 67.0±19.7, p<0.0001. Fatigue had a higher intensity among those with depression than without (49% vs. 51%, with scores of 62.8±16.9 vs. 52.1±19.3, p<0.001) and among those with sleep disorder than without (27% vs. 73%, with scores of 61.2±19.2 vs. 55.9±18.6; p<0.05). A majority of participants (52%) reported experiencing fatigue before their MS diagnosis. Those with lower disability rated fatigue as the most impactful symptom on daily life. The most common factor associated with increased fatigue was heat exposure (82%). Conclusions: In this survey including the novel RMS specific FSIQ-RMS, fatigue occurred in most MS participants and adversely influenced daily functioning. Fatigue remains a major concern for those with MS.