Background: Development of autoimmune neurological disorders after Coronavirus Disease 2019 (COVID-19) has been reported. Though many cases of multiple sclerosis developing after COVID-19 are present in current literature, Neuromyelitis Optica Spectrum Disorder (NMOSD) is much rarer sequela of the disease.Methods: Two cases that meet the international consensus diagnostic criteria for NMOSD were encountered at a regional hospital in West Texas in the same month. Both were preceded by acute SARS-CoV-2 infection and developed newly diagnosed NMOSD with Aquaporin-4 Protein Antibody seropositivity.Results: Case 1 was a 28-year-old Hispanic female who presented with opsoclonus and ophthalmoplegia; Case 2 was a 20-year-old African American female who presented with transverse myelitis. Both patients had no neurological co morbidities or symptoms prior to SARS-CoV-2 infection. Neither of them was vaccinated for COVID-19, and both were of non-Caucasian ethnicity. They presented with a typical features including younger onset, ocular presentation of opsoclonus, negative neuroimaging, no response to steroids, and relapse after a short interval. Conclusion: New developments of NMOSD in previously healthy individuals can be a neurological sequela of COVID-19, especially among unvaccinated individuals. The correlation and pathophysiology of NMOSD after COVID-19 are not fully understood, but molecular mimicry of the virus and cytokine storm are postulated mechanisms. Additional observational studies are needed to further explore the correlation between acute COVID-19 infection and NMOSD.