H2O2 is produced either via a two-electron transfer or as a result of sickling and it is removed by two main antioxidant enzymes: GPx and CAT [18,52,57]. CAT is usually more important than GPx because of its ability to degrade H2O2 without consum- ing cellular reducing equivalents (GSH or NADPH), which is an energy-efficient way of removing H2O2 [41]. There is a discrepancy between studies on SCD CAT levels; some studies have shown decreased CAT activity in transgenic sickle mouse models [56] and likewise in SCD patients [55,58]. In contrast, Manfredini et al. [54] observed increased CAT levels in SCD patients, in agreement with another study done by Das and Nair [52]. The increase in CAT might be a protective effect to scavenge H2O2, whereas the decreased levels might be due to the overwhelming and chronic oxidative stress [59]. An additional hypothesis is that elevated antioxidant enzyme levels in sickle erythrocytes might also be a consequence of higher reticulocyte content in SCD patients’ blood.