To investigate the clinical features of newly-onset central nervous system (CNS) demyelinating disorders post-SARS-CoV-2 infection. Methods: A total of 57 patients with newly diagnosed CNS demyelinating diseases admitted to our department from May 2022 to May 2023 were studied. Among these, 37 individuals who contracted SARS-CoV-2 within a month preceding symptom onset constituted the infection group; meanwhile, 20 patients without prior SARS-CoV-2 exposure formed the control group. Clinical and radiological records of both groups were gathered for comparative assessment, followed by a year-long surveillance. Results: The median time span between SARS-CoV-2 infection and the manifestation of CNS demyelination in the infected group was 13 (7, 20) days. Disparities were observed in specific spinal manifestations and annual recurrence rates (ARR) between the groups; specifically, the infection group exhibited elevated frequencies of limb paralysis (22.1% vs 16.7%, P<0.05) and disturbances in bladder and bowel function (17.6% vs 5.6%, P<0.05) relative to controls (P<0.05), along with a reduced ARR [(0.00 ± 0.35) vs (0.00 ± 0.69), P<0.05]; conversely, no statistically significant disparities emerged in other clinical presentations, neurological evaluations, immunological markers, imaging characteristics, electrophysiological studies, ophthalmological tests, or short-term prognoses across the two groups (P>0.05). Conclusion: While an association exists between SARS-CoV-2 infection and the emergence of CNS demyelinating conditions, the causal link remains undetermined. Clinically, demyelinating patients with and without SARS-CoV-2 infection largely share similar profiles, save for select spinal symptoms and variations in ARR.