The aim of the study was to evaluate the effect of diet supplementation with vitamin E (40 or 250 mg α-tocopheryl acetate · kg⁻¹) and/or vitamin C (0, 200 or 500 mg ascorbic acid · kg⁻¹) for 40 days after weaning at 28 day of age on α-tocopherol concentrations in tissues, oxidative status and immune response in piglets (n = 144; 7.99 ± 0.12 kg). High level of dietary vitamin E addition into piglet diet resulted in increased concentration of α-tocopherol in serum and liver at days 42 and 68 after weaning when compared to the low-dose vitamin E-supplemented groups. Such effect was not found in piglets muscles and fat until day 68. At day 68 the antioxidant status in piglets fed high-dose vitamin E-supplemented diet increased and muscle oxidation (TBARS) decreased mainly at day 68 with no changes in the immune response in comparison to low-dose vitamin E-supplemented groups. Dietary vitamin C supplementation did not affect α-tocopherol levels in serum, liver and muscle, whereas α-tocopherol content in fat tended to be higher in piglets fed diets supplemented with both vitamins at day 68. Dietary vitamin C increased the serum antioxidant power (FRAP) and immunoglobulin (Ig) M tended to be higher at 42 day of age, while at day 68 IgA concentration increased. An interaction effect of both vitamins on the FRAP or muscle TBARS values was not observed; however, IgA increased only in groups fed diets supplemented with vitamin C and low dose of vitamin E. A long-term supplementation of the high-dose vitamin E-enriched diet is recommended for improving the oxidative status of piglets in the post-weaning period. An additional vitamin C-enrichment may have beneficial effects on oxidative status and the immune response, especially if the serum α-tocopherol concentration is close to values of 1 mg · ml⁻¹.