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Abstract Background Vaccination against COVID-19 continues apace, but side-effects, both common and severe, continue to be reported. We report here the first published case of COVID-19 vaccine-related encephalitis. Case presentation A young woman presented with acute neuropsychiatric symptoms following recent ChAdOx1 nCoV-19 vaccination. Extensive investigation did not identify alternative causes. Conclusions This difficult case is here described, including presentation, investigation, and management. Further study on neuropsychiatric side-effects of COVID-19 vaccination, including investigation as to whether there may be a causal link, is required.