Red blood cells (RBCs) are highly specialized cells with a limited metabolic repertoire. However, it has been demonstrated that metabolic processes are affected by the production of reactive oxygen species (ROS), and critical enzymes allied to metabolic pathways can be impaired by redox reactions. Thus, oxidative stress-induced alternations in the metabolic pathways can contribute to cell dysfunction of human RBCs. Herein, we aim to provide an overview on the metabolic pathways of human RBCs, focusing on their pathophysiological relevance and their regulation in oxidative stress-related conditions.