Abstract Introduction: Sickle haemoglobin (HbS) polymerisation perturbs red blood cell (RBC) rheology and drives sickle cell disease (SCD) pathophysiology. Voxelotor is an HbS polymerisation inhibitor that increases haemoglobin (Hb)–oxygen affinity. Methods/Results: In this 48‐week, prospective, single‐centre translational study, 10 children aged 4–11 years with SCD were treated with voxelotor. Improvements in RBC deformability were observed using osmotic/oxygen gradient ektacytometry, with increases in minimal and maximal elongation index and reductions in point of sickling. Increased Hb and reduced markers of haemolysis were also observed. Conclusion: These findings suggest that voxelotor treatment is associated with reduced RBC sickling and haemolysis in children with SCD.