Abstract Extracorporeal membrane oxygenation (ECMO) has been widely used clinically to support heart and/or lung function. ECMO exposes the blood to non-endothelial cell surface and trigger systemic and local inflammatory responses. Monocytes are proved to contribute to ECMO-induced inflammatory responses and infection. In this study, we investigated the inflammatory cytokines secretion of monocytes and explored the possible mechanisms. Materials and Methods Fifty seven patients undergoing ECMO support were enrolled at Beijing Anzhen Hospital, Capital Medical University. Peripheral blood samples from patients were collected into EDTA tubes after the ECMO support days 1, 2, 3, 5 and 7 and post weaning. The ability of monocytes to secret cytokines and the percentage of CD71+ cells were examined by flow cytometry. The effects of CD71+ erythroid cells on the ability of secrete cytokines of monocytes were explored by depleting CD71+ erythroid cells with magnetic beads sorting. The mechanisms of inhibitory effect of CD71+ erythroid on cytokines secretion of monocytes were investigated with Transwell coculture system. Results In patients supported with ECMO, the ability of monocytes to secrete cytokines, TNF-a, IL-6 and IL-1b, was significantly decreased compared with healthy controls. It was accompanied by the increased percentage of CD71+ erythroid cells. Depletion of CD71+ erythroid cells rescued the ability of monocytes to secrete cytokines. CD71+ erythroid cells inhibited the cytokines secretion of monocytes in cell-to-cell contact manner. Conclusion The enriched CD71+ erythroid cells in peripheral blood inhibited inflammatory cytokines secretion of monocytes in cell-to-cell contact manner in patients supported with ECMO.