Voxelotor is a novel hemoglobin polymerization inhibitor which has been demonstrated to reduce hemolysis and improve hemoglobin levels. There have been numerous studies examining the clinical impact of voxelotor in sickle cell disease (SCD) patients, but there are few published reports on the effects of treatment on physical function in patients with SCD. The hypothesis to be tested is that anemic SCD patients will have improvements in performance after 6 months of voxelotor treatment.

Inclusion Criteria:

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Male or female,
4. aged 18-65 years
5. Diagnosis of sickle cell disease with HbSS, HbSc, HbS-beta thalassemia genotypes
6. Hemoglobin level of 6 g/dL - 10.5 g/dL
7. Between 0 and 10 vaso-occlusive (VOC) episodes in previous 12 months
8. Ability to take oral medication and be willing to adhere to the voxelotor regimen
9. For females of reproductive potential, they will be educated to avoid pregnancy during study period and for one month after due to limited data surrounding pregnancy and voxelotor
10. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner
11. Agreement to adhere to Lifestyle Considerations (see section 5.3) throughout study duration

Exclusion Criteria:

1. Hemoglobin results < 6 g/dL or > 10.5 g/dL
2. Patients receiving hydroxyurea who have had a dose change within the prior 3 months
3. Females who are breastfeeding or pregnant
4. Patients who are receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) within 30 days of 6MWT
5. Any form of hepatic dysfunction as demonstrated by alanine aminotransferase (ALT) >4 × ULN or Child-Pugh Class C
6. Acute kidney injury or chronic renal disease with estimated glomerular filtration rate<30mL/min/1.73 m2
7. Current or previous diagnosis of malignancy within the last two years excluding local therapy for non-melanoma skin malignancy
8. Unstable cardiopulmonary disease within the last 6 months prior to study enrollment
9. Any conditions including behavioral or medical that in the opinion of the investigator, may negatively impact informed consent, participation and study interpretation
10. Current use of commercially available voxelotor
11. Prior hypersensitivity to voxelotor or its excipients
12. Patients with baseline gait and other physical impairments that would limit 6MWT and other functional assessment at discretion of the investigator
13. Patients who on day of assessment present with vaso-occlusive crisis or rate their pain greater than 6 on a scale of 1-10 using the Numeric Rating Scale will not be assessed that day and re-screened at the investigator's discretion.