BACKGROUND: Sepsis is a systemic inflammatory response to infection and is one of the leading causes of morbidity and mortality. The second hit after trauma causes increased inflammatory response and multiple organ failure (MOF). The infection which develops after burn injury is a suitable model for a two-hit trauma study. Sepsis causes the release of biochemical mediators, such as Free Oxygen Radicals (FORs), which may lead to lipid peroxidation, which may play a key role in multiple organ failure. In this study, we aimed to investigate the effects of phosphodiesterase (PDE) inhibitors (sildenafil, milrinone, pentoxifylline) and N-acetylcysteine (NAS) on oxidative stress and organ damage in two-hit models.