Inclusion Criteria:  SS or S-β0 major sickle cell syndrome Hemoglobin level < 9 g/dL Aged 18 years or older Stable dose for at least 3 months if treated with HU, EPO, angiotensin-converting enzyme (ACE) or inhibitor/angiotensin receptor blocker (ARB) therapy; at least after 6 months after initiating HU treatment Patient with social security Female patient must have a negative serum pregnancy test (betaHCG within 72 hours prior to start of treatment) or evidence of post-menopausal status Effective methods of birth control (e.g., condom, spermicidal gel, oral contraceptive, indwelling intrauterine device, hormonal implant/patch, injections, approved cervical ring) or abstinence from screening through 4 weeks after last Voxelotor dose.  Exclusion Criteria:  Patient meeting Hydroxyurea indications of treatment (recurrent painful vaso-occlusive crises, including acute chest syndrome) at screening; Or if HU treatment is indicated at screening but inappropriate (e.g. hematologic toxicity antecedent) or patient refuses HU. Patients in chronic transfusion program or transfused < 3 months before enrolment Patient with severe organ involvement: hepatic (TP <50%), renal (eGFR<30 ml / ml/1.73m2 according to CKD/EPI or cardiac (LVEF <45%) Transplant patients. Pregnancy. Breast feeding patients Homeless patient Patient deprived of liberty by judicial or administrative decision or patient under guardianship Patient unable to understand the purpose and conditions of the study and unable to give consent Chronic use of NSAIDs (more than 10 days by month) Auto immune disease or infection not controlled or cancer VIH, HBV, HCV current infection Prior drug hypersensitivity to Voxelotor or excipients Known allergy or hypersensitivity to imaging contrast product Ongoing therapeutic study