The present study aimed to evaluate blood redox status and acute phase protein profile throughout two pharmacological treatment protocols for pyometra bitches, employing aglepristone either as a monotherapy or in combination with prostaglandin. A prospective study was conducted in 10 open-cervix pyometra bitches assigned to two groups: aglepristone (n = 5; subcutaneous injections of aglepristone on days 1, 2, and 8 after diagnosis) and aglepristone + prostaglandin (n = 5, aglepristone coupled with daily injections of cloprostenol from days 1 to 7). Blood samples were collected daily for the liver profile (alanine aminotransferase—ALT, alkaline phosphatase, and albumin), acute phase proteins (C-reactive protein-CRP, haptoglobin, and serum amyloid-A), and redox analysis [antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx) and reduced glutathione (GSH), oxidative stress (TBARS), and protein oxidation]. In the aglepristone group, there was increase in albumin concentration and SOD, while protein oxidation and GSH decreased progressively throughout treatment. The aglepristone + prostaglandin group had lower ALT levels but higher lipid peroxidation, GPx, and CRP. In conclusion, the combined use of prostaglandin modified the profile of oxidative markers, antioxidant enzymes, and C-reactive protein, thereby preventing the assessment of treatment efficacy. Conversely, albumin concentration proved a sensitive marker of therapeutic effectiveness in both treatment protocols for pyometra bitches.