Sickle cell disease (SCD) is a genetic disorder charac- terized by a chronic inflammatory process, and new biomarkers have been studied as promising molecules for understanding the inflammation in its pathophy- siology. The hemolysis and the release of molecules associated to the hemoglobin (Hb) catabolism, such as free Hb, iron, and heme, generate an oxidant envi- ronment with production of reactive oxygen and ni- trogen species. The immune system plays a very im- portant role in the inflammation, with cells secreting pro-inflammatory cytokines and chemokines. There is also a nitric oxide (NO) resistance state, with an impaired NO bioactivity, leading to a vascular dys- function; activation of platelet, leukocytes, erythro- cytes, and endothelial cells, with expression of adhe- sion molecules and its ligands, and several receptors, that altogether participate at inflammatory process. During inflammation, there is an increase of dendritic cells (DCs) expressing toll like receptors (TLR), but the role of DCs and TLR in SCD pathogenesis is un-clear. Also, there are molecules contributing for en-hance the endothelium dysfunction, such as homo-cysteine that has been associated with vascular com-plications in the pathology of other diseases and it may contribute to the vascular complications pre-sented by SCD patients. Circulating microparticules (MPs) levels are augmented in several diseases and have been described in SCD, where cells membrane compounds are associated to cell’s thrombotic and coagulation state, such as tissue factor and phos-phatidylserine (PS), which may contribute to endo-thelial dysfunction. The knowledge of all these bio-markers may contribute to new therapeutic approach discover, improving SCD patient life quality.