EVs impact transfusion outcomes by modulating immune and inflammatory responses. Acting as lipid mediators and expressing adhesion molecules, EVs contribute to immune signaling via cytokines, DAMPs, and antigen-presenting molecules. In RBC, EVs accumulate during storage and are linked to endothelial cell (EC) activation, increased thrombotic risk, and tissue inflammation — especially under existing inflammatory conditions. While their effect on circulating immune cells is limited, they strongly activate tissue-resident immune and EC. In PCs, platelet-derived EVs and other cell-specific EVs also emerge. Certain EV subtypes express CD27, CD70, CD39, and HLA antigens, altering T-cell, B-cell, and monocyte activity. These immunomodulatory effects may contribute to transfusion-related immunomodulation and alloimmunization.