Sepsis remains a leading cause of mortality worldwide, and understanding endothelial damage is crucial for improving patient outcomes. Endothelial dysfunction in sepsis contributes to coagulopathy, increased capillary permeability, and vasoplegia, but the interplay between these processes remains underexplored. The study aims to evaluate the clinical relationship between those factors due to sepsis-induced endothelial damage. A prospective single-center study on 75 community-acquired septic patients admitted to an Intermediate Care Unit. The Sepsis-Induced Coagulopathy (SIC) score, serum albumin (as a surrogate for capillary leak), and Total Peripheral Resistance Index (TPRI) (as a surrogate for vasoplegia) were assessed. Structural Equation Modeling (SEM) explored the relationship between variables, hypothesizing a common latent factor (endothelial damage). Principal Component Analysis assessed the shared variance among variables. The mean SIC score was 3.4 (SD 1.3), with 44% of patients affected. TPRI and albumin had mean values of 1954 (SD 738) and 2.58 (SD 0.59), respectively, both negatively correlated with SIC: TPRI -0.263 ( = 0.023) and albumin -0.454 ( < 0.001). SEM showed SIC, albumin, and TPRI are associated with a latent factor (endothelial damage), explaining 68% of the variance (CFI = 1.000, RMSEA = 0.000). Albumin was inversely correlated ( = 0.004), and TPRI was significantly associated ( = 0.003). This pilot study suggests that coagulopathy, increased vascular permeability, and vasoplegia may be clinically interrelated manifestations of endothelial injury in sepsis. These findings support the feasibility of modeling a unified pathophysiological construct using accessible bedside data, potentially guiding future individualized approaches in sepsis management.