This study is a pilot, open-label, single-arm study to evaluate the effect of the sickle cell medication voxelotor on exercise capacity, as measured by cardiopulmonary exercise testing (CPET) in patients 12 years of age and older with sickle cell anemia (SCA).

This study will assess exercise capacity by cardiopulmonary exercise testing (CPET) before and after 8 weeks of voxelotor therapy.

Patients with genetically severe forms of sickle cell disease, including Hgb SS, Hgb S beta 0 thalassemia, Hgb SC Harlem, etc., age 12 or older, with stable Hgb and Hgb F will be recruited. Enrolled subjects will have study labs drawn, undergo baseline CPET in the exercise lab, then take voxelotor 1500mg daily for 2 months, followed by repeat study labs and a second CPET. Each subject's CPET results before and after voxelotor will be compared, and the study labs before and after voxelotor will be compared. Each subject will be compared to him/herself.

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, age > 12 years
4. In good general health as evidenced by medical history and diagnosed with a genetically severe form of sickle cell anemia (Hgb SS, Hgb S beta 0 thalassemia, Hgb SCHarlem, and others)
5. Patients who are on Hydroxyurea need to be on a stable dose for at least 3 months without anticipated change in dosing until the study is completed.
6. Ability to take oral medication and willingness to adhere to daily voxelotor and 2 CPETs at scheduled intervals.
7. For females of reproductive potential who are sexually active: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 30 days after the end of study.
8. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner

Exclusion Criteria:

1. Patients on chronic transfusions or who received a transfusion within last 8 weeks
2. Patients who had hospitalization for vaso-occlusive crisis or acute chest syndrome within 30 days prior to informed consent/assent.
3. Patients who have screening alanine aminotransferase (ALT) > 4X upper limit of normal
4. Patients who suffer from physical inactivity attributable to clinically significant musculoskeletal, cardiovascular, or respiratory comorbidities
5. Patients already taking commercially available voxelotor
6. Prior hypersensitivity to voxelotor or excipients.
7. Pregnant patients