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Post-COVID-19 syndrome (PCS) is frequently associated with fatigue and cognitive dysfunction, while underlying mechanisms remain unclear. We report a 44-year-old male with persistent symptoms following SARS-CoV-2 infection, including severe cognitive and motor fatigue, word-finding difficulties, and impaired concentration. Neuropsychological testing revealed marked deficits in alertness, attention, fluency, and processing speed. Serum analysis demonstrated anti-VGLUT2 autoantibodies. IVIG therapy yielded subjective but no objective improvement. This appears to be the first PCS case associated with VGLUT2 autoantibodies and raises the hypothesis of a potential pathophysiological link that requires confirmation in larger cohorts.