Sickle cell disease (SCD) is a genetic blood disorder that has profound effects on the brain. Chronic anemia combined with both macro- and microvascular perfusion abnormalities that arise from stenosis or occlusion of blood vessels increased blood viscosity, adherence of red blood cells to the vascular endothelium, and impaired autoregulatory mechanisms in SCD patients all culminate in susceptibility to cerebral infarction. Indeed, the risk of stroke is 250 times higher in children with SCD than in the general population. Unfortunately, while transcranial Doppler ultrasound (TCD) has been widely clinically adopted to longitudinally monitor macrovascular perfusion in these patients, routine clinical screening of microvascular perfusion abnormalities is challenging with current modalities (e.g., positron emission tomography and magnetic resonance imaging) given their high-cost, requirement for sedation in children <6 year, and need for trained personnel. We assess the feasibility of a low-cost, noninvasive optical technique known as diffuse correlation spectroscopy (DCS) to quantify an index of resting-state cortical cerebral blood flow (BFI) in 11 children with SCD along with 11 sex- and age-matched healthy controls. As expected, BFI was significantly higher in SCD subjects compared to healthy controls (p  <  0.001). Within SCD subjects, BFI was inversely proportional to resting-state arterial hemoglobin levels (p  =  0.012), consistent with expected anemia-induced compensatory vasodilation that aims to maintain adequate oxygen delivery to the tissue. Further, in a subset of patients measured with TCD (n  =  7), DCS-measured blood flow was correlated with TCD-measured blood flow velocity in middle cerebral artery (R_s  =  0.68), although the trend was not statistically significant (p  =  0.11). These results are consistent with those of several previous studies using traditional neuroimaging techniques, suggesting that DCS may be a promising low-cost tool for assessment of tissue-level CBF in pediatric SCD.