This study examined the impact of early weaning on antioxidant function in piglets. A total of 40 Duroc × Landrace × Large White, 21-day-old piglets (half male and half female) were divided into suckling groups (SG) and weaning groups (WG). Piglets in WG were weaned at the 21st day, while the piglets in SG continued to get breastfed. Eight piglets from each group were randomly selected and slaughtered at 24th-day (SG3, WG3) and 28th-day old (SG7, WG7). The body weight, liver index, hepatocyte morphology, antioxidant enzymes activity, gene expression of antioxidant enzymes, and Nrf2 signaling in the liver of piglets were measured. The results showed that weaning caused decreased body weight (p < 0.01), lower liver weight (p < 0.01), and decreased the liver organ index (p < 0.05) of piglets. The area and size of hepatocytes in the WG group was smaller than that in the SG group (p < 0.05). We also observed that weaning reduced the activity of superoxide dismutase (SOD) and catalase (CAT) (p < 0.05) in the liver of piglets. Relative to the SG3 group, the gene expression of GSH-Px in liver of WG3 was significantly reduced (p < 0.05). The gene expression of Nrf2 in the SG3 group was higher than that in the WG3 group (p < 0.01). The gene expression of NQO1 in the SG7 group was higher than that in the WG7 group (p < 0.05). In conclusion, weaning resulted in lower weight, slowed liver development, and reduced antioxidant enzymes activity, thereby impairing liver antioxidant function and suppressing piglet growth.