Copper is the most essential trace element in the animal body. Nano-sized copper particles have been widely used in a number of different animal species in modern medicinal practice. The present study was designed to examine the effect of dietary copper sulfate/(CuSO4) and nano copper supplementation on serum antioxidant capacity of weaning piglets. A total of 28 Duroc piglets (21 days, and weighing ~7 kg) were randomly divided into three equal groups. The control group (n=4) was administered with a normal standard diet; however the CuSO4 (n=12) and nano copper (n=12) groups were treated with 50, 100 and 200 mg/kg/day body weight, respectively. After 28 days, blood serum copper-zinc superoxide dismutase (CuZn-SOD), ceruloplasmin (CP), malondialdehyde (MDA), myeloperoxidase (MPO), total antioxidant capacity (T-AOC), peroxidase (POD), nitric oxide (NO), nitric oxide synthase (NOS), hydrogen peroxide (H2O2) and inhibition of hydroxyl radical (CIHR) were analyzed from all groups. The results indicated that nano copper supplementation has significant (P less than 0.05) effect on the serum antioxidant capability as compared to dietary CuSO4 group in weaned piglets. Nano-size copper 100 mg/kg/day supplementation was confirmed to improve the immunity level by strengthening the antioxidant capacity of weaning piglets. Dietary supplementation with 100 mg/kg body weight nano copper could be a potential substitute for weaned piglets.