The generation of anaphylatoxins, particularly C5a, is important in extracorporeal circulation therapies such as granulocyte/monocyte apheresis, which activates the complement system and elevates C5a levels. However, no side effects of granulocyte/monocyte apheresis using cellulose acetate beads have been reported. To investigate the mechanism of complement activation, we prepared plasma from cellulose acetate bead-treated blood (P-CAB) and compared it with zymosan-activated plasma (ZAP). Anaphylaxis activity was measured by skin test, and the activity of carboxypeptidase, which inactivates C5a, was measured by colorimetric assay. Pro-carboxypeptidase R and neutrophil elastase concentrations were measured by enzyme-linked immunosorbent assay. Although C5a was generated in P-CAB, the anaphylaxis activity of P-CAB was lower than that of ZAP. Carboxypeptidase activity and pro-carboxypeptidase R levels were suppressed in P-CAB, but not in ZAP. Furthermore, neutrophil elastase levels increased in P-CAB. The decreases in carboxypeptidase activity and inactivation of anaphylatoxin were inhibited by a neutrophil elastase inhibitor. These results suggest that cellulose acetate beads initiate the activation of carboxypeptidase R via elastase release, thereby inducing the inactivation of anaphylatoxin.