Sickle cell disease (SCD) is associated with stroke1 and slower processing2. Slower processing in the absence of stroke may be related to hypoxic-ischaemic white-matter (WM) injury3. Cognitive assessments and tract-based spatial statistics analyses using diffusion tensor imaging (DTI), were conducted in 84 patients with SCD, stratified by degree of hypoxic-anaemic exposure. Processing speed indices (PSI) were related to WM integrity, and there were differences in PSI and WM integrity as a function of daytime oxygen-desaturation, but not SCI. The results provide links between oxygen desaturation, PSI, and WM integrity, and may indicate amelioration of function by interventions that reduce hypoxic exposure.