Bergeron, N., Robert, C. and Guay, F. 2014. Antioxidant status and inflammatory response in weanling piglets fed diets supplemented with arginine and zinc. Can. J. Anim. Sci. 94: 87-97. Dietary supplementation with zinc oxide (Zn oxide) and arginine (Arg) is known to improve growth in weanling piglets. The mechanism of action is not yet well understood, although antioxidant effects and inflammatory responses may be involved. This experiment was conducted to evaluate the effects of Zn and Arg supplementation on the antioxidant status and inflammatory response of piglets. Thirty-two 20-d-old weanling piglets were placed for 12 d on diets supplemented or not with Zn (2500 mg Zn oxide kg^-1) and Arg (1%), designated ZN0ARG0, ZN2500ARG0, ZN0ARG1 and ZN2500ARG1. On day 12, blood samples were taken before and 3 h after intra-peritoneal injection of lipopolysaccharide (LPS; 10 µg kg^-1). The piglets were euthanized just after the second blood sample, and samples of mucosae were taken from the jejunum and ileum for determination of mRNA expression and morphological observation. Zn supplementation decreased plasma malondialdehyde measured before LPS injection (P<0.05). Arg supplementation increased the ferric-reducing ability of plasma (indicator of antioxidant status) measured after LPS injection (P<0.05). Piglets fed Zn-supplemented diets had lower total plasma superoxide-dismutase (SOD) activity (P<0.05) but higher plasma tumour necrosis factor-α (P<0.05) after LPS injection. Zinc-supplemented diets increased metallothionein-1 expression and total antioxidant capacity in the ileum and jejunum (P<0.05) and decreased interleukin-10 expression (P<0.05) in the ileum. In the jejunum, the combination of Zn and Arg supplementation increased villus height (Arg×Zn, P<0.05). These results indicate that Zn may reduce systemic oxidation and improve the antioxidant status in the jejunal and ileal mucosae. However, Zn and Arg supplementation did not appear to act synergistically to enhance antioxidant status or reduce inflammation in weanling piglets.