Sepsis is a complex inflammatory syndrome with diverse etiology and wide spectrum of severity. Several researchers have linked reactive oxygen species (ROS) and reactive nitrogen species (RNS) with the onset, progression and outcome of sepsis, both in pre-clinical and in clinical studies. ROS/RNS are important signaling molecules but its overproduction must be avoided by organism, otherwise oxidative stress takes place. Even so, the use of antioxidant as treatment in sepsis constitutes a challenge, with both null and encouraging results. In this review, it will be summarized the role of free radicals in the onset, progression and outcome of sepsis, as well as its participation in organ failure and cardiovascular collapse. Experimental treatments that may interfere in oxidative stress in sepsis will also be contemplated.