Background: Heart failure (HF) has been associated with changes in inflammatory and oxidative-stress biomarkers. This study aimed to evaluate the changes of a panel of inflammatory and oxidative stress biomarker in dogs with different stages of HF and its relation with the severity of the disease and the echocardiographic changes. Dogs with HF as a result of myxomatous mitral valve degeneration or dilated cardiomyopathy were included. A total of 29 dogs were classified as stage-A (healthy), B (asymptomatic dogs), C (symptomatic dogs) and D (dogs with end-stage-HF) according to the ACVIM-staging-system. Serum cytokines, and inflammatory and oxidative stress markers were evaluated.Results: KC-like as an inflammatory cytokine was significantly increased in dogs of stage-C (P<0.01) and -D (P<0.05) compared with stage-A and -B. Stage-D Dogs showed significantly higher serum CRP and Hp (P<0.05) but lower serum anti-oxidant capacity (PON1, TEAC, CUPRAC, and thiol) compared to stage-A and -B (P<0.05). After the treatment, serum levels of CRP, Hp and KC-like decreased but serum anti-oxidant levels increased compared to their pre-treatment values. Left ventricular dimension and LA/Ao ratio correlated positively with CRP, MCP-1, and KC-like but negatively with PON1, GM-CSF, IL-7 and antioxidant biomarkers (P<0.01). Conclusion: our results indicated that dogs with advanced-stages of HF show increases in positive acute-phase proteins and selected inflammatory cytokines (KC-like), and decreases in antioxidant biomarkers, indicating that inflammation and oxidative-stress act as collaborative partners in the pathogenesis of HF. Some of these biomarkers of inflammation and oxidative stress could be tested as new biomarkers to monitor the severity of the disease and the effect of treatment.