The influence of psychosocial stress on antioxidant enzymes (AOE) in the central nervous system is associated with mood disorders. To unravel systemic effects of psychosocial stress we aimed to investigate AOE activity in peripheral organs and erythrocytes of peripubertal rats due to social isolation during peripuberty. Social play with peers during this period is highly rewarding activity abundant in the young of most mammalian species. Absence of peer social support is associated with depression. Male peripubertal Wistar Han rats were either group-housed (3/cage) or single-housed (1/cage) during early postnatal (P) days (P29-P36) and early-to-late (P29-P43) adolescence. To assess whether social environment influences AOE activity to additional stress, half of the animals from both age groups underwent overnight fasting. Tissue samples (liver, kidney, heart) and erythrocytes were collected at P36 and P43. AOE activity (glutathione peroxidase, superoxide dismutases, catalase, and glutathione reductase) was measured spectrophotometrically. Glutathione reductase and catalase were unaffected by social isolation in both age groups in all examined organs. The influence of social isolation on the AOE activity after the overnight fasting was tissue- and enzyme-specific and was dependent on the maturational phase. Erythrocyte superoxide dismutase was the only enzyme that showed increased activity due to the social isolation, regardless of the presence of an additional stress. Social isolation in adolescence modifies AOE activity in peripheral organs and erythrocytes, shaping the response of the enzymes to additional stress. Erythrocyte superoxide dismutase could be a biomarker of social stress-related mood disorders in adolescence.