We have assessed cerebral blood flow (CBF), venous T2, and hematocrit (Hct) in mice to characterize the performance of MR markers of cerebral physiology in wildtype (WT) mice and the Townes transgenic mouse model of Sickle Cell Disease (SCD). SCD mice exhibited increased CBF, decreased venous T2, and decreased Hct compared to matched WT mice. Combining MR measures of CBF and venous T2 with Hct measurement improved the disease-specific differentiation. Test-retest variability was approximately 20% for CBF and venous T2 and 10% for Hct. Methods employed in this study are fully translational to the clinic.