Sickle cell diseases (SCD) are characterized by the presence of hemoglobin S, hemolytic anemia and vascular occlusion. Silent infarcts in SCD patients is strongly associated with an increased stroke risk and progressive cognitive decline. In this study we used 99mTc-ECD single photon emission computerized tomography (SPECT) in order to detect early abnormalities of brain perfusion in neurologically asymptomatic adult SCD patients. We recruited 42 SCD (27 females and 15 males, mean age of 33.4±10.55, range 17–60 years) from the Hematology and Hemotherapy Center of the University of Campinas.The SCD types were distributed as follows: 33 HbSS (14 males and 19 females), 6 HbSC (1 male and 5 females) and 3 HbSBeta (3 females). Mean steady state hemoglobin level measured in the period of up to 2 weeks before or after imaging acquisition was 8.5g/dl (±1.73; 5.2–13.5) and mean hematocrit was 25.1% (±4.85; 15.6–38.5). The group of patients with SCD was compared to a group of control healthy subjects (29 females and 20 males with mean age 31 years ±8; 25–49) recruited within the local community, who were submitted to the same imaging protocol used in the patients.The study was approved by the National Ethical Committee Board and informed-write consent was obtained from all patients. The inclusion criteria for this study was to be at least 17 years old, have a precise clinical and laboratory diagnosis of any SCD, do not have stroke previously and be on regular follow-up in the clinic. All of them were submitted to a standard protocol of brain SPECT image acquisition. Reconstructed transaxial datasets were converted into ANALYZE format and corrected for the orthogonal plane of acquisition using MRIcro software. Voxel-based analysis was performed using SPM2 (Wellcome Department of Cognitive Neurology). Images were spatially normalized to standard anatomical template defined in the atlas of Talairach and Tournoux. The normalized smoothed images underwent group comparison of regional tracer uptake using paired t-test. Contrasts were defined in order to estimate the probability of each voxel to have an increased or decreased tracer uptake in images from patients with SCD compared to images from the normal control group. Reduced tracer uptake was observed in many areas of the brain when compared to normal controls. These areas corresponded predominantly to watershed regions and other brain areas supplied by micro vasculature. We observed a reduced tracer uptake in the central basal forebrain, which includes the basal ganglia and thalami, the anterior frontal region and the watershed region of the temporo-parietal-occipital transition. These regions are to be considered the most significant hypoperfused areas (false discovery rate correction of p<0.05).The findings of our study demonstrate that neurologically asymptomatic SCD patients exhibit a pattern of reduced 99mTc-ECD tracer uptake demonstrated by SPECT. Early diagnosis of such cerebral vasculopathy has prognostic implications and can be determinant in considering therapeutic alternatives to avoid increasing in brain lesion load and progressive disability.