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Background: While imaging biomarkers guide stroke prevention strategies in children with sickle cell (SC) disease, none have been adequately studied in adults. High oxygen extraction (OEF) predicts stroke in non-SC adults with carotid occlusion, while low oxygen metabolism (CMRO2) predicts tissue at imminent risk in acute ischemic stroke. We hypothesized that metrics of cerebral metabolism: (1) differ between SC adults with and without stroke and (2) correlate with infarct burden.Methods: A prospective MRI study enrolled 37 adults (28 ± 8 yr) from SC clinic into 4 groups: (1) 9 age/race matched healthy controls, (2) 6 SC adults without infarcts, (3) 15 SC adults with infarcts (infarct volume 7.4 ± 17.5 ml), and (4) 7 SC adults on chronic transfusions (Tx) (infarct volume 3.6 ± 6.6 ml). Arterial spin labelling and asymmetric spin echo measured voxel-wise cerebral blood flow (CBF) and OEF. CMRO2 = CBF x OEF x blood oxygen content. Infarcts were delineated on FLAIR. OEF, CBF, and CMRO2 (excluding infarcted tissue) were compared: between groups 1-3 (Kruskal-Wallis) and in group 4 between pre- and post-tx scans (Signed Rank). An ROI defined by high OEF within the deep white matter (a region at high stroke risk in SC) was applied to group 3. OEF, CBF, and CMRO2 within the ROI were correlated with hemispheric infarct volume (IV) (Spearman’s ρ).Results: Whole brain OEF showed a stepwise increase from controls, to SC adults without stroke, to SC adults with stroke (P<.001). SC adults on chronic Tx had intermediate OEF, with lowering of OEF post-Tx (Fig A). CBF and CMRO2 were similar for SC adults with and without stroke (Fig B, C). High OEF and low CBF/CMRO2 in the ROI correlated with hemispheric infarct burden: IV vs. OEF (ρ=.40, P=.043); IV vs. CBF (ρ=-.61, P=.002); and IV vs. CMRO2 (ρ=-.50, P=.016).Conclusion: Global OEF holds promise to stratify stroke risk in SC disease. Regional metrics of cerebral oxygen metabolism may indicate tissue-specific metabolic stress at imminent risk of infarction.