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The objective of this experiment was to investigate the influence of weaning stress and an antioxidant blend on gut health and free radical metabolism in postweaning pigs. A total of 96 pigs from 12 litters were randomly divided by litter to 3 groups with 4 litters each. The control group and the weaning group were fed the basal diet, and the antioxidant group was fed the basal diet supplemented with an antioxidant blend. The control group was suckling normally during the experimental period and the other 2 treatments were weaned at 21 d of age. Morphology in different parts of the intestines was used as a measure of intestinal barrier function. Activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and the concentrations of malondialdehyde (MDA), NO, H2O2, and O2 were measured in serum. Activities of the digestive enzymes, including sucrase, maltase, amylase, lipase, and pepsin, were measured at 24 d of age for all treatments. Gene expressions of free radicals, digestive enzymes, or antioxidant enzymes were selected for quantitative reverse transcription-PCR analyses. Results showed that weaning resulted in reductions (P < 0.05) in the villus height and width, and activity of digestive enzymes. Activity of SOD decreased (P < 0.05) and the concentrations of MDA, NO, and H2O2 increased (P < 0.05) after weaning. The expression results indicated that the genes related to the antioxidant enzymes and digestive enzymes were down regulated (P < 0.05) after weaning. Tumor protein 53, which regulates reactive oxygen-species generation, tended to increase (P < 0.10) in the weaning group. The concentration of PPARγ coactivator-1α (PGC-1α), which plays an important protective role against oxidative stress by regulating the expression of mitochondrial antioxidants, was reduced (P < 0.05) in weaning pigs and increased (P < 0.01) in antioxidant pigs compared with the control pigs. Results indicated that intestinal dysfunction occurred after weaning and there was an inhibition of the antioxidant system. The antioxidant blend has the potential to prevent free radical-induced damage and suppress oxidative stress by modulating the expressions of tumor protein 53 and PGC-1α genes.