Canine distemper virus (CDV) causes a multisystemic disease with central nervous system involvement in dogs. Little is known about the role of immuno-inflammatory and redox-state biomarkers in the pathogenesis and diagnosis of naturally occurring CDV infection. Thus, the objectives of this study were: 1) to evaluate the potential differences in a profile of cytokines/chemokines, and inflammatory and redox-status biomarkers in serum between dogs with CDV-infection and healthy dogs, and 2) possible correlations between serum/blood and cerebrospinal fluid (CSF) of these biomarkers in dogs with CDV-infection. Two groups of dogs were designed: 10 with CDV-infection, and 10 healthy. A total of 13 cytokines/chemokines, 3 inflammatory (C-reactive protein [CRP], haptoglobin [Hp], and butyrylcholinesterase [BChE]) and 3 antioxidants of redox status (cupric reducing antioxidant capacity [CUPRAC], Thiol, and ferric reducing ability of plasma [FRAP]) were analyzed in serum and CSF samples. Serum IL-7, IL-8, MCP-1, CRP, Hp, FRAP and Thiol levels were higher (P < 0.05) in dogs with CDV compared to controls. There were significant (P < 0.05) correlations only in IL-6 and MCP-1 between CSF and serum. In conclusion, deregulated immune response, raised inflammation, and imbalances of redox homeostasis and antioxidant defense status may play role in the pathophysiological mechanism of neurological form of CDV-infection. The combination of clinical features and cytokine biomarkers (IL-7, IL-8 and MCP-1) might facilitate clinical diagnosis for neural involvement in dogs with CDV. Some cytokine/chemokine (IL-6 and MCP-1) in CSF are highly correlated with those of serum, indicating that serum samples could reflect the possible changes of these analytes in CSF.