Low RBC deformability under NOI and HOI is associated with laboratory markers of severe clinical phenotype. An increase of 1% in NOI is associated with 5.68 × 106/μL higher reticulocyte count (P = .02, A), 0.1 gm% lower hemoglobin (P = .001, C), and 0.33% higher dense RBCs (P < .001, F). One percent increase in HOI is associated with 6.59 × 106/μL higher ARC (P < .001, B), 0.04% lower hemoglobin (P = .05, E), 88/μL higher ANC (P < .001, C), and 0.1% higher dense RBCs (P = .04, G). (H) MIRCA NOI and HOI readouts were collected for a subset of individuals with SCD (n = 91) also run on LoRRca oxygen-gradient ektacytometry. Statistically significant standardized effect sizes of the association between MIRCA and LoRRca biomarkers with traditional laboratory markers of SCD severity (Hb, g/dL), ARC (109/μL), ANC (103/μL), DRBC (%) are reported after controlling for age, genotype, and transfusion status. The standardized effect sizes reflect 1 SD change in MIRCA or LoRRca values with 1 SD increase in traditional laboratory markers.