Erythrocytes are continuously exposed to free radicals (FR) injury due to their high cellular oxygen concentration and heme iron. The autoxidation of oxyhaemoglobin to methaemoglobin, generating superoxide anion radical, represents the main source of FR in erythrocytes. The erythrocyte membrane is particularly sensitive to oxidative damage due to its high polyunsaturated fatty acid content, and hence, it represents an important system to evaluate the effect of oxidative stress (OS). Information on how red cells OS is triggered and mechanisms of erythrocytes oxidative pressure from plasma may provide a partial answer to questions about the causes of the anaemia of prematurity and about red cell involvement in hypoxia. The recent insights about the mechanism of oxidative injury of red cells and the evidence of relationships between erythrocyte, OS and hypoxia suggest that increased haemolysis is induced by severe hypoxia and acidosis in the perinatal period.