BACKGROUND: Glycocalyx degradation is implicated in endothelial damage and microcirculatory dysfunction in sepsis, whereas the effectiveness of plasma syndecan-1 levels and sublingual microcirculatory parameters in evaluating sepsis's prognosis has not yet been determined. This study aims to track their dynamic changes and investigate the prognostic utility of these indexes in sepsis. METHODS: In this prospective study conducted at the First Affiliated Hospital of Sun Yat-sen University, blood samples were collected from adult surgical septic patients within 2 days after intensive care unit admission measuring plasma syndecan-1 concentrations. Relevant sublingual microcirculatory parameters were also obtained simultaneously. Additionally, capillary refill time and serum lactate levels were recorded. The primary outcome was 30-day mortality. RESULTS: Of the 74 patients enrolled, the 30-day mortality rate was 35.1%. Significantly, higher syndecan-1 levels were observed in nonsurvivors at baseline, day 1, and day 2 (62.43 [37.37 and 103.16] vs. 97.24 [52.95 and 186.40] ng/mL and p = 0.035
62.22 [41.50 and 87.52] vs. 96.71 [60.82 and 176.00] ng/mL and p = 0.009
and 56.03 [39.16 and 94.48] vs. 87.69 [72.52 and 159.70] ng/mL and p = 0.005, respectively). High syndecan-1 levels (≥121 ng/mL) were associated with lower survival rates (p = 0.002) and an increase exceeding 8 ng/mL within 2 days indicated a higher mortality risk (p = 0.0075). Syndecan-1 levels displayed satisfactory prognostic capability (AUC: 0.7056), whereas combining syndecan-1 and blood lactate demonstrated the highest predictive ability for 30-day survival (AUC: 0.7726). CONCLUSIONS: Plasma syndecan-1 levels effectively predict sepsis prognosis, with higher baseline levels or increasing trends indicating worse outcomes. Combining syndecan-1 with blood lactate enhances predictive accuracy for 30-day mortality in sepsis. TRIAL REGISTRATION: This study registered in China on December 31, 2021 at Chinese Clinical Trial Registry (ChiCTR2100055066).