Dengue virus infection presents a wide spectrum of manifestations including asymptomatic condition, dengue fever (DF), or severe forms, such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) in affected individuals. The early prediction of severe dengue in patients without any warning signs who may later develop severe DHF is very important to choose appropriate intensive supportive therapy since available vaccines for immunization are yet to be approved. Severe dengue responses include T and B cell activation and apoptosis, cytokine storm, hematologic disorders and complement activation. Cytokines, complement and other unidentified factors may transiently act on the endothelium and alter normal fluid barrier function of the endothelial cells and cause plasma leakage. In this review, the host factors such as activated immune and endothelial cells and their products which can be utilized as biomarkers for severe dengue disease are discussed.