Purpose: In this study, our purpose was to investigate effect of oxidative stress composing in isolated rats on erythrocyte deformability and antioxidant system, considering importance of mechanical, and biochemical properties of erythrocytes in efficiency of blood circulation Material and Methods: Fourty Sprague-Dawley rats were divided into two groups according to their ages; where one of them consisted of 2 months old rats and the other 12 months old rats. Then, randomly selected ten rats in each group were isolated separately in a cage and hold 12/12 hour light-dark cycle lasting 21 days. Blood samples were collected at the end of the 21st day, and superoxide dismutase (SOD), catalase (CAT) activities and malondialdehyde (MDA) levels were measured spectrophotometrically. Changes in plasma nitric oxide level were determined by Griess method depending on total nitrite-nitrate. In addition, relative filtration rate (RFR), relative filtration time (RFT) and relative resistance (Rrel) of the erythrocytes were calculated as the indexes of erythrocyte deformability. Results: The SOD and CAT levels were found significantly lower in both of young and adult isolated rats when compared to the young and adult control groups. The nitric oxide levels were also found significantly lower in the young and adult isolated rats when compared to their control groups. The peroxidation of the lipids were also decreased by social isolation, in the erythrocyte membrane of both young and adult isolated rats compared to the controls. The indexes of erythrocyte deformability, RFR was found significantly higher, whereas the RFT was significantly lower in young and adult isolated rats compared to the young and adult controls. However, the Rrel of the erythrocytes were not altered dramatically. Conclusion: As a consequence, our data reveals that the social isolation causes a lack of plasma nitric oxide levels in the socially isolated rats and probably due to this decrease in one of the major oxidants for the erythrocyte membrane results in the decreased lipid peroxidation. Furthermore, our results reveal that the social isolation stress causes alterations in the antioxidant defense system and these alteration results in the changes in erythrocyte deformability reflecting that some tissue perfusion problems can occur with long term and repeated loneliness and especially in the early stages of the life span