Silent cerebral infarcts are the most common neurologic injury in patients with sickle cell disease (SCD). In this study, we compared T2 -relaxation under spin tagging (TRUST) and susceptibility-based oximetry (SBO) techniques in a cohort of SCD patients compared to healthy control subjects. We observed opposite trends in oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) in SCD patients compared to controls using TRUST and SBO methods. High OEF measured by TRUST technique lead to very high supraphysiologic CMRO2 values. We conclude that SBO method is more reliable in measuring OEF and CMRO2 in patients with SCD.