In this review, we will focus on how ROS produced by NOX enzymes, in contribution with Hb S autoxidation within sickle RBCs, affect interactions of these cells, with the vascular endothelium and other blood cells promoting vaso-occlusion, activation of coagulation, hemolysis-related anemia, activation of the complement system, endothelial dysfunction and tissue injury, and further inflammation, all of which promote SCD vascular pathology. Here, GSTM1 is linked to Schnyder corneal dystrophy.