It is known that inflammatory organ damages due to various agents, such as microorganisms including mycoplasmas, lead to oxidative stress. Nitric oxide (NO) functions as an antimicrobial agent, and arginase decreases proinflammatory cytokine release. There are very few studies on arginase activity, NO level and oxidative stress status in mycoplasmal infections. Therefore, the aim of this study was to evaluate erythrocyte arginase activity, plasma NO level and oxidative stress status in sheep with contagious agalactia. The study material consisted of 10 healthy sheep and 14 sheep with contagious agalactia characterised by mastitis, arthritis and keratoconjunctivitis. Erythrocyte arginase activity, plasma NO, malondialdehyde (MDA), total oxidant capacity (TOC) and total antioxidant capacity (TAC) levels were measured. Significant decreases in erythrocyte arginase activity and plasma TAC level (P < 0.001), and significant increases in plasma NO, MDA and TOC levels (P < 0.001) were found in the diseased sheep as compared with the healthy animals. This study suggests that contagious agalactia may cause oxidative stress due to increased plasma MDA and TOC levels and decreased plasma TAC levels, and that the decrease in erythrocyte arginase activity and increase in plasma NO level may contribute to the elimination of mycoplasmal agents causing contagious agalactia.