The coronavirus disease-19 (COVID-19) pandemic leaded to inevitable expeditious vaccine rollout without sufficient safety profile. Especially, severe acute respiratory syndrome coronavirus 2 infection has known to induce overreacted immune responses such as releasing of proteinase-3 and myeloperoxidase (MPO) by neutrophil. This overreacted immune response leads to the concern of the development of autoimmune diseases after COVID-19 vaccination. We report the case of de novo MPO-associated systemic vasculitis involving central nervous system following heterogeneous mRNA1273 COVID-19 booster vaccination.