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.