Studies on inflammatory markers, endothelial activation, and bleeding during extracorporeal membrane oxygenation (ECMO) are lacking. Blood samples were prospectively collected after ECMO initiation from 150 adult patients who underwent ECMO for respiratory failure between 2018 and 2021. After excluding patients who died early (within 48 h), 132 patients were finally included. Their tumor necrosis factor-alpha (TNF-α), tissue factor (TF), soluble thrombomodulin (sTM), and E-selectin levels were measured. A Cox proportional hazards regression model was used to estimate the hazard ratio for hemorrhagic complications during ECMO. The 132 patients were divided into hemorrhagic (n= 23, H group) and non-complication (n= 109, N group) groups. The sequential organ failure assessment score, hemoglobin level, and ECMO type were included as covariates in all Cox models to exclude the effects of clinical factors. After adjusting for these factors, initial TNF-α, TF, sTM, E-selectin, and activated protein C levels were significantly associated with hemorrhagic complications (allp< 0.001). TNF-α, TF, and E-selectin better predicted hemorrhagic complications than the model that included only the aforementioned clinical factors (clinical factors only (area under the curve [AUC]: 0.804), reference; TNF-α (AUC: 0.914); TF (AUC: 0.915); E-selectin (AUC: 0.869)). Conclusions: TNF-α levels were significantly predictive of hemorrhagic complications during ECMO.