Background: The feline leukemia virus (FeLV) is clinically important retroviruses that infect domestic and wild feline worldwide, affecting more than 3 million cats representing a great risk for premature death. Some studies have demonstrated that oxidative stress, as well as the adenosinergic system, exert an important role in the pathogenesis of viral diseases. Oxidative stress is considered a disturbance in the antioxidant/oxidant status in favor of the excessive generation or lower removal of free radicals. Therefore, the aim of this study was to evaluate whether changes on the adenosinergic system and oxidative stress occurred in cats positives for feline leukemia virus (FeLV).Materials, Methods & Results: Forty-nine serum samples of cats (between 4 months and 13 years of age) seen at the Veterinary Hospital of the University of Santa Catarina State (UDESC - Lages, SC, Brazil) were used. Blood samples were collected from the jugular vein and stored in tubes without anticoagulant to obtain serum. An aliquot was used to detect both viral infections using the kit SNAP FIV/FeLV, that detects the p27 protein from FeLV and antibodies against the p24 protein from FIV. The test was performed according the manufacture’s recommendations. Based on this result, this study involved 20 FeLV negative cats, 20 FeLV positive symptomatic cats, and 9 FeLV positives asymptomatic cats. Serum samples were used to determine the activities of adenosine deaminase (ADA) and glutathione-S-transferase (GST), as well as thiobarbituric acid reactive substances (TBARS) and reactive oxygen levels (ROS). Seric ADA and GST activities, as well as TBARS (lipid peroxidation) and ROS (free radical) levels were determined spectrophotometrically according to the specific method. Seric ADA activity was increased in symptomatic animals compared to negatives and also to asymptomatic positive animals, and the same was observed for seric TBARS levels. On the other hand, GST activity decreased in the symptomatic and asymptomatic groups compared to the negative control group. No difference was observed regarding seric ROS levels.Discussion: The upregulation of seric ADA activity observed in this present study could contribute to the inflammatory process since it would decrease seric levels of Ado, a nucleoside with anti-inflammatory effects. Lipids, especially the polyunsaturated fatty acids, are sensitive to oxidation by free radicals, generating MDA, and cause to increase of TBARS levels. A significant negative correlation between lipid peroxidation and ADA activity in kidney samples of rats experimentally infected by protozoan, and these authors demonstrated that increase on lipid peroxidation is linked to decreased ADA activity. The reduction on seric GST activity can be explained since the antioxidant enzyme was unable to remove the excess of peroxides and superoxide anion, resulting on decreased cellular antioxidant activity. Based on these evidences, it is possible to conclude that symptomatic FeLV cats showed an upregulation on seric ADA activity associated to the impairment of the immune response, contributing to inflammatory processes. Moreover, FeLV symptomatic cats showed damage to lipids and an impairment on antioxidant/oxidant status, alterations compatible to oxidative stress and oxidative damage. In summary, these alterations contribute to the pathophysiology of FeLV infection, and can be used as markers of this disease.