**Abstract**

Red blood cells (RBCs) are continuously exposed to oxidative stress (OS), mainly due to their primary function as oxygen carriers. Since RBC is a unique cell, without nucleus or other organelles, it presents a very special metabolism and a highly efficient antioxidant system to face OS conditions. Hemoglobin and RBC membrane are the major targets of oxidative modifications when RBC antioxidant capacity is overwhelmed. Fortunately, non-enzymatic agents, such as glutathione, and enzymatic agents, namely, several peroxidases, such as catalase, glutathione peroxidase and peroxiredoxin 2, are able to prevent OS damage. Although these peroxidases are mainly cytosolic enzymes, evidence exists about their association to the RBC membrane. So far, it appears that the relative importance of the three enzymes is related to hydrogen peroxide levels within the RBC. In this chapter, we will focus on the importance of these peroxidases in the RBC's defense against OS mainly in the RBC cytosol and also the interplay between them and the RBC membrane. The potential role of their binding to the membrane will also be addressed.

**Keywords:** erythrocyte peroxidases, erythrocyte membrane, hemoglobin, oxidative stress, erythrocyte antioxidant system
