BACKGROUND: Low sleep quality, cardiac autonomic dysfunction and poor quality of life are some of the most prevalent symptoms in people with Multiple Sclerosis (MS). In addition to the progression of the disease, these symptoms are aggravated by physical inactivity. Therefore, home confinement due to COVID-19 pandemic restrictions could further worsen these symptoms. This study aims to analyze the effect of home confinement on objective and subjective sleep quality, cardiac autonomic control based on heart rate variability (HRV), and health-related quality of life in people with MS. METHODS: Actigraphic and subjective sleep quality (Karolinska Sleep Diary, KSD), HRV (Polar-H7), and quality of life (Multiple Sclerosis Quality of Life-54) were measured before and after 2 months of home confinement in 17 people with MS (7:10 men/women; age: 43.41+/-10.88 years; body mass index: 24.87+/-3.31鈥痥g/m(2); Expanded Disability Status Scale: 2.85+/-1.34 a.u.). RESULTS: Actigraphic sleep quality (sleep efficiency: ES=1.27, p鈥?鈥?.01, sleep time: ES=0.81, p鈥?鈥?.01) and subjective sleep quality (sleep quality: ES=-0.34, p鈥?鈥?.05), sleep comfort: ES=0.60; p鈥?鈥?.03, ease of falling asleep: ES=0.70; p鈥?鈥?.01, ease of waking up: ES=0.87, p<0.01, and having enough sleep: ES=0.87, p<0.01) significantly decreased after home confinement. No differences were observed in HRV or quality of life variables (p鈥?/=鈥?.13). CONCLUSIONS: Home confinement has worsened the sleep quality, but not in cardiac autonomic control or quality of life, in people with MS. These data highlight the importance of implementing home physical training programs in this population when situations similar to home confinement occur, thus minimizing the negative effects of physical inactivity and their associated comorbidities.