Hemophagocytic lymphohistiocytosis (HLH) is a rare, severe hyperinflammatory disease characterized by overproduction of cytokines and hemophagocytosis of hematopoietic cells, resulting in multiorgan failure. Prompt treatment initiation is essential for patient survival. The coronavirus disease 2019 (COVID-19) pandemic has led to the rapid development of several vaccines, including BNT162b2 by Pfizer-BioNTech. Few cases of immune-mediated complications of COVID-19 and its vaccines have been reported, characterized by persistent stimulation of the immune system, resembling HLH. We report the case of a 21-year-old man with secondary HLH following a second dose of the BNT162b2 vaccine. The patient did not have primary HLH or other contributors to secondary HLH and met the HLH-2004 diagnostic criteria. He was safely treated with steroid pulse therapy alone, without etoposide, cyclosporin, or immunoglobulins, which are recommended for pediatric patients. Physicians need to be aware of such severe complications following a second dose of the COVID-19 vaccine.