Sickle Cell Anemia SCA is a hemolytic deficiency that is typified by strangely formed sickles red blood cells that are expelled from circulation at expanded rates, leading to anemia. It is caused by inheritance of hemoglobin Hb that has mutated, which compared to adult normal Hb, contains a single amino acid substitution, where at the sixth residue valine substitutes glutamic acid in the Hb tetramer in both of the two B chains. For SCA patients, chronic inflammatory conditions are linked to high levels of inflammation markers, including cytokines and adhesion molecules. Cytokines are a group of small proteins that are essential in cell signaling. The immuno regulatory molecules known as anti-inflammatory cytokines control the response of pro inflammatory and have gained attention recently as anti-inflammatory mediator in SCA patients. The most interesting anti-inflammatory cytokines are IL10, IL 4, IL 27, and IL 37. This a case-control study aimed to measure the concentrations of the antiinflammatory cytokines in 3 groups, SCA patients without the use of any medication, SCA patients under Hydroxy Urea therapy SCAHU, and healthy people male and female in the general Saudi population, using a total of 78 chosen subjects. Using ELISA kits, cytokine levels were measured in the plasma of the patients. The results of the study indicated that anti inflammatory cytokines were elevated in SCA and SCAHU patients when compared to the control P equal to 0.001, and there were no significant differences between SCA and SCAHU patients. The anti inflammatory cytokines, including IL 27 and IL 37, that were detected for the first time in SCA patients in KSA in this research, have a role in keeping patients in a steadystate and reducing inflammation, therefore more research to understand the roles of these cytokines in SCA pathology of is essential to allow the development of effective therapies to treat this disease.