The goal of this study is to identify non-invasive optical hemodynamic biomarkers that can index laboratory hematology measurements in sickle cell disease (SCD). We acquired frequency-domain NIRS (FD-NIRS) and diffuse correlation spectroscopy (DCS) data from the forearms and foreheads of 17 participants in a randomized, double-blind, placebo-controlled trial evaluating effects of isoquercetin (IQ) on thromboinflammation in SCD. We observed multiple, significant correlations between optical and hematology biomarkers including cerebral tissue oxygen saturation (StO2) and hematocrit (HCT); oxyhemoglobin ([O2Hb]) recovery rate and intercellular adhesion molecule 1 (ICAM-1); and blood flow index (BFI) reperfusion rate and coagulation index (CI). The potential of these non-invasive optical biomarkers for assessing vascular pathophysiology for the management of SCD warrants further exploration.