Blood transfusions are often administered for secondary stroke prevention in adults with sickle cell anemia (SCA). We utilized noninvasive MRI methods to evaluate how oxygen extraction fraction (OEF) and cerebral blood flow (CBF) adjust after transfusion in adults with SCA. OEF reduced on average, while CBF did not change significantly. The OEF reduction paralleled increases in hematocrit but was unrelated to the reduction in hemoglobin-S. This implies that most patients receiving transfusions operate near autoregulatory reserve capacity even after transfusion, and improving oxygen delivery by increasing hematocrit can be visualized noninvasively with OEF-MRI.