Chronic inflammation and reduced blood levels of omega-3 fatty acids (n−3) are known characteristics of sickle cell disease (SCD).The anti-inflammatory properties of n−3 fatty acids are well recognized.Omega-3 treated (n=24), hydroxyurea (HU) treated (n=18), and n−3 untreated (n=21) homozygous SCD patients (HbSS) and healthy (HbAA) controls (n=25) matched for age (5–16years), gender and socioeconomic status were studied. According to age (5–10) or (11–16) years, two or three capsules containing 277.8mg docosahexaenoic (DHA) and 39.0mg eicosapentaenoic (EPA) or high oleic acid placebo (41%) were assigned to n−3 treated and n−3 untreated groups, respectively. Hydroxyurea treated group was on dosage more than 20mg/kg/day. The effect of supplementation on systemic and blood cell markers of inflammation was investigated.The n−3 treated group had higher levels of DHA and EPA (p<0.001) and lower white blood cell count and monocyte integrin (p<0.05) compared with the n−3 untreated. No difference was detected between the two groups regarding C-reactive protein, granulocytes integrin and selectin, plasma tumour necrosis factor-α and interleukin-10. The n−3 treated group had lowered nuclear factor-kappa B (NF-κB) gene expression compared to n−3 untreated and HU treated groups (p<0.05).This study provides evidence that supplementation with n−3 fatty acids may ameliorate inflammation and blood cell adhesion in patients with SCD.