Data of recent research suggest that patients with sickle cell disease(SCD) have a persistent low grade inflammation due to subclinical microvascular ischemic events that lead to tissue injury. This is followed by release of inflammatory cytokines, endothelial cell activation and enhanced adhesion molecule expression that promotes the abdominal red blood cell - endothelial adherence and results to vascular complications of SCD. The objective of this study was to measure circulating indicators of inflammation and endothelial cell activation in children with SCD during the symptom - free steady state and a vaso-obstructive crisis. Thirty three such children aged 5-17,5 yrs (mean 11,8 yrs) were studied during the steady state and 10/33 during a crisis as well. Twenty apparently healthy children served as controls. Of the 33 children with SCD 11 had no crises and 22 had two or more crises per year. All patients were receiving the same treatment during crises. Levels of circulating inflammatory cytokines IL-1β, IL-6 and of soluble L- selectin (adhesion molecule of leukocytes) were measured as indicators of inflammation. Levels of soluble VCAM - 1 AND E - selectin (adhesion molecules of endothelial cells) were measured as indicators of endothelial cell activation. Measurements were done using an enzyme quantitative immunoassay(Quantikine R & D Systems). All patients were found to have increased levels of serum IL-1β, IL-6, sL-selectin, VCAM-1 and sE-selectin compared to controls (4,5 vs 0,8, 16 vs 0,3, 2303 vs 950, 1810 vs 550, 102 vs 46 respectively). The difference in the median values of all parameters between the two groups was statistically significant (p<0,05). All the above parameters were further elevated during crises (slightly to 1,5 times above values of the steady state) in the 10/33 patients studied. No correlation was found between the mean values of the above parameters and the number of crises per year. These findings indicate that a chronic inflammation and a persistent endothelial cell activation exist in children with SCD regardless of the clinical expression of vaso - obstructive episodes. This data open new horizons for adopting new strategies in the prevention and treatment of SCD vascular complications.