Longitudinal changes of serum angiopoietin 1 (Ang-1) and angiopoietin 2 (Ang-2) associated with endothelial stability in dengue patients with different disease stages were studied. Serum Ang-1 and Ang-2 levels were measured in confirmed dengue fever (DF) patients on admission (DFA,  = 40) and discharge (DFD,  = 20); in dengue hemorrhagic fever (DHF) patients on admission (DHFA,  = 40), at critical stage (DHFC,  = 36), and on discharge (DHFD,  = 20); and in healthy controls (HC,  = 25). DHFC had the highest serum Ang-2 and lowest Ang-1 levels compared to DFA, DHFA, and HC ( < 0.050). The ratio of serum Ang-2/Ang-1 in DHFC was the highest among all study categories tested ( < 0.001). Significant positive correlations were observed between serum Ang-1 and platelet count in DHFA (Pearson  = 0.653, < 0.001) and between Ang-1 and pulse pressure in DHFC (  = 0.636, = 0.001). Using a cutoff value of 1.01 for the Ang-2/Ang-1 ratio for DHFC, a sensitivity of 83.2% and a specificity of 81.2% discerning DF from DHF were obtained. Therefore, serum Ang-2/Ang-1 could be used as a biomarker for endothelial dysfunction in severe dengue at the critical stage.