Canine monocytic ehrlichiosis (CME) is an important hemoprotozoan disease of dogs associated with anemia, leucopenia, and thrombocytopenia. The present study was conducted with the aim of assessing the status of oxidative/nitrosative stress and apoptosis in naturally occurring cases of chronic canine monocytic ehrlichiosis, to investigate potential of darbepoietin alpha in ameliorating oxidative/nitrosative stress and apoptosis associated with CME and to assess the impact of darbepoietin alpha administration on clinical outcome in chronic canine monocytic ehrlichiosis. Thirty naturally occurring cases of chronic CME were allotted randomly in two treatment groups, groups I and II. Animals in group I were treated with doxycycline @10 mg/kg, PO, sid, for 28 days, and other supportive therapy. Whereas, animals in group II received darbapoietin alpha in addition to doxycycline and supportive therapy. Six apparently healthy dogs acted as healthy control. All these animals were monitored closely till 28 days of post treatment. Normocytic normochromic anemia, thrombocytopenia, decreased leukocyte count, increased levels of blood urea nitrogen (BUN), creatinine, alanine transaminase (ALT), and alkaline phosphatase (SAP) were observed in dogs suffering from chronic CME. There was significant increase in the levels of lipid peroxidation (LPO), nitric oxide (NO), and apoptosis percentage in dogs suffering from chronic CME. Levels of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase were significantly reduced in dogs suffering from chronic CME. Rapid improvement in the hematological values, oxidative, and nitrosative stress markers and percent apoptosis were observed in group II as compared to group I. Rapid clinical recovery and reduced hospital stay were observed in animals belonging to group II as compared to group I. No adverse effects of darbepoietin alpha administration were observed in the present study.