To protect people from coronavirus disease 2019 (COVID-19), various types of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and administered. Adverse reactions to COVID-19 vaccines include various local and systemic adverse reactions which may occur immediately or weeks later. Here we report a case of systemic inflammatory response syndrome induced by COVID-19 vaccine. A 65-year-old man with a history of hypertension presented with 5 days of fever. On admission, he was febrile to 38.3℃ with mild dyspnea when experiencing febrile sensation. Six days ago, he was vaccinated with the BNT162b2 mRNA COVID-19 vaccine. Fever with chill developed one day after vaccination and persisted. Chest radiography and a CT scan showed bilateral pleural effusion. Abdomen CT showed interstitial edematous pancreatitis at pancreas tail and perinephric infiltration. PET/CT revealed diffuse hypermetabolic infiltration or activity in mediastinal fat tissue, pericardial and peritoneal thickening. Laboratory Results documented leukocytosis, elevated levels of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and C-reactive protein. There was no evidence of possible infectious diseases or rheumatic diseases after a full examination and consultation with the specialists. With the administration of high-dose oral corticosteroids, fever and pleural effusion disappeared gradually. These findings suggest systemic inflammatory response syndrome induced by COVID-19 mRNA vaccine.