Mortality rates associated with myocardial dysfunction due to sepsis and septic shock are generally high across the world. Although symptomatic therapies are employed in an attempt to cope with the resulting complications, there is an urgent need for effective and reliable novel agents regulating oxidative stress and the inflammatory process in cardiac damage to be discovered and developed. The present study focused on the antioxidant and anti-inflammatory effects of perindopril for the purpose of preventing the adverse effects of sepsis on the myocardium and developing new alternatives in treatment. The control group received only saline solution via the oral route for four days. The second group underwent cecal ligation puncture (CLP), and the third underwent CLP and received PER (2 mg/kg). Rats in the third group received 2 mg/kg PER p.o. from four days before induction of sepsis. TBARS, total -SH, IL-1β, IL-6 and 8-OHdG levels increased in the CLP groups. In contrast, PER (2 mg/kg) administered reduced the levels of biochemical parameters, apart from -SH, in rat heart tissues, and lowered 8-OHdG immunopositivity. The data from this study show that impairment of the antioxidant/antioxidant balance and inflammatory cytokine levels in favor of inflammation in heart tissue under septic conditions results in severe tissue damage. Per administration before sepsis was shown to exhibit antioxidant and anti-inflammatory properties by reducing these effects. This in turn increased the importance of PER as new evidence of its protective effects in heart tissue.