BACKGROUND: Blood transfusion is associated with an increased risk of organ damage, infection, and alloimmunity. Neutrophil extracellular traps (NETs) are extracellular chromatin fibers decorated with neutrophil granular proteins that have been linked to cytotoxicity, thrombosis, and autoimmunity. We questioned whether neutrophils in blood products release NETs during storage and thus could contribute to adverse reactions from blood transfusions. STUDY DESIGN AND METHODS: We analyzed supernatants and blood smears of human red blood cell (RBC) units that either were or were not leukoreduced before storage for markers of NETs. RESULTS: We identified extracellular DNA, which was associated with histones and myeloperoxidase, a marker of neutrophil granules, in supernatants and blood smears of nonleukoreduced RBC units. These markers of NETs were absent in leukoreduced RBC units. Importantly, NETs passed through blood transfusion filters and could therefore potentially be infused into patients. CONCLUSIONS: Our studies indicate that NETs are liberated during storage of nonleukoreduced RBC units. Future studies should address whether NETs in RBC units could potentially contribute to transfusion-associated complications.