Inclusion Criteria:  Sickle cell disease (all genotypes) Children, adolescents and young adults between ages 6 to 21 years In a steady disease state and not in the midst of any acute complication other than VOC due to sickle cell disease at study entry For female of childbearing potential, a negative urine pregnancy test and using an adequate method of contraception, or denies sexual activity Subjects or parents or legal guardian of the subject who are willing and able to sign and provide consent and assent (where appropriate for the age of the child).  Exclusion Criteria:  Current pain lasting >3 days >6 hospital admissions in the prior year History of opioid dependence/substance abuse Has been on a clinical trial of a new therapy for sickle cell disease within the last 3 months Presence of any other complication related to sickle cell disease such as splenic sequestration, hepatic sequestration, stroke, avascular necrosis of the hip/shoulder, acute priapism, renal dysfunction, dactylitis, acute chest syndrome and other major medical conditions or organ dysfunction Severe anemia (hemoglobin <6 g/dL) History of red blood cell transfusion within the last 30 days Systemic steroid therapy within the last 48 hours Pregnancy or lactation (subjects must have a negative urine pregnancy test)  Serum creatinine levels:  Age 6 to 13 years >0.9 mg/dL Age 14 to 17 years >1.0 mg/dL Age >18 years >1.5 mg/dL Report of fever (>38°C) within last 48 hours Presence of acute chest syndrome, sepsis, bacterial infection, hemodynamic instability  Subjects with inability to have parental assent given (ages 6 to 17 years) or consent (ages 18 through 21 years).  Note: Parents or legal guardians can provide consent for subjects who are unable to provide assent (eg, sleepy or preoccupied by their pain).  History of allergic reaction to L-citrulline product Medications that are known to be contra-indicated with use of L-citrulline History of diabetes. Subjects with a baseline prothrombin time International Normalized ratio (INR) >2.0. Received any blood products within 3 weeks of the screening visit. Unreliable venous access The PI considers that the subject will be unable to comply with the study requirements.