Abstract: This disclosure relates to use of anti-IL-1? antibodies (e.g., canakinumab or gevokizumab) in a therapy treating, preventing, reducing, or alleviating one or more manifestations and complications in individuals suffering from sickle cell disease (including, e.g., homozygous HbS gene carriers, heterozygotes with sickle-beta-thalassemia with an SCD supporting combination of HbS gene and beta-tha1 gene, an individual with one sickle cell gene and one null allele, or an individual with hemoglobin sickle cell disease), optionally in combination with an additional therapeutic agent. Such manifestations and complications include, but are not limited to: pain, fatigue, hospitalization, poor sleep quality, work or school absences, narcotic use, acute or chronic blood transfusion therapy, acute chest syndrome, bone infarct, avascular necrosis, osteonecrosis, stroke, priapism, infarction of penis, a cardiovascular disorder, growth delay, stunted growth, low body mass index (BMI), low body weight, and organ damage.