This study is a pilot, phase II, open-label study of the angiotensin II receptor blocker, losartan, in patients with Sickle Cell Disease (SCD) 6 years or older for 12 months. The investigators will enroll 24 patients with SCD over the course of 1 year with a goal to complete all study procedures in 2 years. The short-term goal is to obtain clinical pilot data regarding the safety and efficacy of losartan in stabilizing or decreasing extracellular volume fraction (ECV) after 12 months of therapy.

Inclusion Criteria:

1. 6 years old or older
2. Diagnosis of HbSS or Sbeta0-thalassemia
3. Ability to cooperate with and undergo CMR without sedation or anesthesia
4. Ability to cooperate with and undergo echocardiogram without sedation or anesthesia
5. Patients who are on a stable dose of sickle cell disease-modifying therapy: Hydroxyurea, Voxelotor, L-Glutamine, or Crizanlizumab, for 3 months prior to enrollment will be eligible.

Exclusion Criteria:

1. Current chronic transfusion therapy. Patients who received a simple transfusion for an acute event will be eligible 3 months after completion of transfusion
2. SCD genotypes other than specified in inclusion criteria
3. Any contraindication to CMR such as metallic implants
4. Inability to cooperate with CMR or echocardiography imaging
5. Known congenital heart disease
6. Estimated GFR ≤ to 30 mL/min/1.73 m2 by creatinine clearance
7. Pregnant or lactating females or females of child-bearing potential who are unable to use a medically accepted form of contraception throughout the study
8. Treatment with a renin-angiotensin pathway inhibitor during the 2 weeks prior to enrollment
9. Hypersensitivity to angiotensin receptor II blockers
10. Hyperkalemia (K>5.5 mEq/L) on a non-hemolyzed sample despite low-potassium diet
11. Hepatic dysfunction defined as serum ALT > 5x the upper normal limit for age
12. Current lithium therapy
13. Chronic daily use of NSAID
14. HIV infection.