Background <p>Autoimmune nodopathy is a distinct entity characterized by antibodies targeting nodal/paranodal proteins like neurofascin-186 (NF186), leading to conduction defects and neurological dysfunction. This report highlights a unique case of autoimmune nodopathy with anti-NF186 antibodies following SARS-CoV-2 infection.</p> Case presentation <p>A 47-year-old female developed acute limb numbness and weakness ten days post-COVID-19 diagnosis, which progressed to respiratory muscle paralysis necessitating mechanical ventilation. Initial treatments with intravenous immunoglobulin and steroids were ineffective. Diagnosis of autoimmune nodopathy with anti-NF186 antibodies was confirmed through clinical examination, electromyography (EMG), and serum antibody testing using cell-based assays. The patient showed partial improvement with plasma exchange therapy and achieved stability after rituximab treatment, consistent with the typical treatment response pattern for anti-NF186 autoimmune nodopathy. Notably, re-infection with SARS-CoV-2 did not exacerbate her symptoms, and a gradual recovery of muscle strength was observed over time, with the patient regaining substantial independence in daily activities by November 2023.</p> Conclusions <p>This case represents the first reported occurrence of anti-NF186 autoimmune nodopathy following SARS-CoV-2 infection, underscoring the potential link between viral triggers and autoimmune neurological disorders. It emphasizes the importance of testing for specific nodal/paranodal antibodies in post-COVID neurological presentations and highlights the superior efficacy of plasma exchange and B-cell depleting therapies over conventional treatments in managing nodopathies.</p>