Red blood cells are the largest number of cells in blood. Apart from transporting oxygen and carbon dioxide, they also regulate the immune responses. It has been confirmed that red blood cells can play a role in clearing immune complex, promoting phagocytosis, and presenting antigen through immune adhesion.They can also regulate the immune response by participating in the oxidative stress or interacting with the other lymphocytes. Furthermore, when pathogens invading, the host will exert anti-infective immune response and also induce inflammatory response, causing a series of immunopathological injuries, which may bring changes to the red blood cells' maturation process, their morphology, and functionality. This review summarizes recent progresses on the roles and mechanisms of red blood cells in anti-infectious immunity, providing theoretical basis for revealing pathogenesis and exploring therapeutic targets.