SUMMARY: Objective: To determine if the complement system, a potent mediator of inflammation, contributes to haemolysis during red blood cell (RBC) storage. Background: RBCs in storage undergo structural and biochemical changes that may result in adverse patient outcomes post-transfusion. Complement activation on leukodepletion and during storage may contribute to the RBC storage lesion. Methods/Materials: We performed a cross-sectional analysis of aliquots of leukoreduced RBC units, stored for 1-6weeks, for the levels of C3a, C5a, Bb, iC3b, C4d and C5b-9 [membrane attack complex (MAC)] by enzyme-linked immunosorbent assay (ELISA). Results: We observed that only MAC levels significantly increased in RBC units as a function of storage time. We also observed that the level of C5b-9 bound to RBCs increased as a function of storage time. Conclusion: MAC levels increased over time, suggesting that MAC is the primary complement-mediated contributor to changes in stored RBCs. Inhibition of the terminal complement pathway may stabilise RBC functionality and extend shelf life. © 2014 British Blood Transfusion Society.