Introduction: In the context of coronavirus disease 2019 (COVID-19) pandemic, patients with neuromyelitisoptica spectrum disorder (NMOSD) are vulnerable to develop COVID-19 due to the immunosuppressive therapy. The objective of this study is to describe a known case of NMOSD on rituximab who experienced 2 episodes of COVID-19. Case Report: A 25-year-old woman, a known case of NMOSD on rituximab was diagnosed with asymptomatic COVID-19. Eight months later, following her last infusion of rituximab, she developed moderate COVID-19. After a partial recovery, she exhibited exacerbation of respiratory symptoms leading to readmission and invasive oxygenation. She was eventually discharged home after 31 days. Her monthly neurological evaluation did not reveal evidence of disease activity. She later received intravenous immunoglobulin and the decision was made to start rituximab again. Conclusions:Our case raises the possibility of persistent virus shedding and reactivation of severe acute respiratory syndrome coronavirus-2 in a patient with NMOSD and rituximab therapy. We aimed to emphasize a precise consideration of the management of patients with NMOSD during the COVID-19 pandemic.