The study of the biology of red blood cells has led to revolutionary changes in the understanding of its physiological role. It turned out that these «simple oxygen carriers» are direct participants and regulators of innate immunity reactions. Red blood cells have a unique electrochemical bactericidal mechanism - oxycytosis - based on their ability to acquire an additional triboelectric charge in the mobile medium of the bloodstream and agglutinate circulating bacteria. At the same time, binding to the surface of red blood cells causes the release of reactive oxygen species with antibacterial activity from oxygenated hemoglobin. The bacteria killed in this way cease to be retained on the surface of the red blood cell, return to the blood plasma, after which they are captured by Kupffer cells in the liver and macrophages in the spleen. The participation of red blood cells in immune system reactions is also associated with the ability to bind endogenous and exogenous inflammatory molecules, including chemokines, nucleic acids and components of pathogens, to secrete lipid mediators, etc. The participants in the reactions of innate immunity are the multiscale internal structures of red blood cells (hemoglobin, heme, globins, various alarmins) that can induce and control the development of inflammatory protective and pathological reactions. Under certain conditions, the implementation of protection mechanisms initiated by red blood cells can also cause unwanted destructive responses to infection. In general, depending on the microenvironment, red blood cells can either support anti-inflammatory conditions or promote immune activation. The information presented in this review provides an understanding of the role of red blood cells in the generalization of infections, the pathogenetic role of hemolysis and extracellular hemoglobin in conditions of ischemia/reperfusion. Further research in this area will help identify new therapeutic targets and increase the effectiveness of the treatment of many serious, life-threatening conditions and diseases. Literature was searched using the original publications and databases PubMed, MedLine, Scopus, Google Scholar, etc.