Plasma levels of three soluble inducible adhesion molecules, namely: intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1) and endothelial leucocyte adhesion molecule-1 (sELAM-1) or sE-selectin and the pro-inflammatory cytokine, tumour necrosis factor-alpha (TNF-alpha) were measured in well-defined clinical groups of children with severe and uncomplicated malaria. The goal of the study was to investigate the role of these molecules in immunopathogenic processes associated with severe malaria in Cameroonian children. Results showed significantly increased plasma concentrations of sICAM-1, sVCAM-1 and sE-selectin in children with severe malaria compared to those with uncomplicated malaria and healthy children (P<0.001). TNF-alpha levels increased significantly in children with severe malaria, approximately 2-folds compared to those with uncomplicated malaria and about 3-folds compared to healthy children (P<0.001). More importantly, levels of TNF-alpha strongly correlated with those of the three adhesion molecules and were significantly associated with increased risk of death (P=0.03). In addition, children who died from severe malaria showed higher mean levels of all measured factors compared to those who recovered, with significant differences observed with sICAM-1 (P<0.001) and sE-selectin (P=0.002). Furthermore, children with severe malarial anemia relative to those without, showed significantly elevated levels of the three soluble molecules; and sICAM-1 was significantly associated with increased risk of severe anemia. Taken together, these results confirm the role of TNF-alpha and the three adhesion molecules in pathogenic processes associated with severe malaria in children, and suggest an association between sICAM-1 and severe malarial anemia.