This study was focused to identify the link between oxidative stress and senescence of erythrocytes in vivo. To elucidate this mechanism, various modification of RBC membrane proteins and lipids were analyzed invitro, exposing them to oxidative stress and the results were compared with the changes observed in erythrocytes undergoing senescence in vivo. The other objective was to confirm the mechanism of autoantibody mediated removal of aged RBCs. Our results established that increased lipid peroxidation products, followed by the enhanced damage of RBC membrane protein caused increased RBC membrane protein carbonylation, to normal red cells exposed to the in vitro Fe2+ & ascorbate induced oxidative stress. It was presumable that these changes were mediated by hydroxyl (ȮH) radicals. Further, similar changes were also seen in percoll gradient age fractionated high density aged RBCs.