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Enteroviruses are a frequent source of infection and among the most common central nervous system viral pathogens. Enteroviruses - in particular, the Coxsackie B viruses - are a known cause of myocarditis. Rituximab is a genetically engineered chimeric anti-CD20 monoclonal antibody. Many reports in the literature suggest a higher risk of infection following repeated rituximab therapy, including viral infection. However, observations of enterovirus-related myocarditis in the context of rituximab treatment are scarce. The authors describe the case of a patient with neuromyelitis optica spectrum disorder who developed severe and fatal enterovirus-related myocarditis after rituximab therapy with a difficult differential diagnosis of autoimmune or giant-cell myocarditis. This case highlights the importance of complete diagnostic workup in difficult cases of myocarditis, including endomyocardial biopsies., Competing Interests: Disclosure: The authors have no conflicts of interest to declare., (Copyright © 2021, Radcliffe Cardiology.)