Background: Plasma leakage is a key manifestation of severe dengue, but current recommended diagnostic methods by the World Health Organization (WHO) have several limitations. Endothelial cells (ECs) activation and dysfunction are known to play a central role in plasma leakage. Endocan, a proteoglycan produced by activated ECs, has been shown to correlate with disease severity in dengue infection. This study aimed to evaluate endocan as a potential marker of plasma leakage in dengue infection. Methods: This retrospective cohort study utilized data from the International Study on Biomarkers and Gene Expression Patterns in Patients with Dengue Virus Infection (INVEST), collected from 2010 to 2011 at Cipto Mangunkusumo Hospital, Jakarta, Indonesia. Endocan levels were measured by ELISA and plasma leakage was diagnosed with ultrasonography (USG). Receiver Operating Characteristic (ROC) curve analysis was performed to determine the endocan cut-off level for detecting plasma leakage. Correlation tests were conducted to examine the relationships between endocan, hematocrit, delta hematocrit, and albumin levels. Data were analyzed using GraphPad Prism versi 5.0 for Windows and SPSS version 28. Results: Among 64 patients ((31 dengue fever (DF) and 33 dengue hemorrhagic fever (DHF)), significant differences in endocan levels, thrombocyte count, delta hematocrit, and albumin were found between DF and DHF patients. The area under the curve (AUC) for endocan was 0.83 (95% (CI): 0.73–0.93). A cut-off value of 1.63 ng/mL for endocan demonstrated a sensitivity of 66.7%, specificity of 90.3%, positive predictive value of 88%, and negative predictive value of 71.8%. Furthermore, a negative correlation was found between endocan and albumin levels during the critical phase of dengue (r: -0,4; p: 0,001). Conclusion: We observed a significant increase in endocan levels, mainly during the critical phase of dengue patients with plasma leakage. Our findings indicate that endocan could serve as a novel marker for detecting plasma leakage in dengue patients, demonstrating high specificity. Nevertheless, further validation studies in other populations are necessary to confirm the role of endocan as a marker for plasma leakage in dengue infections. © The Author(s) 2026.