In this study, we revealed that sepsis‐induced lactate production induced EC proinflammatory and coagulation activation‐associated lung injury via H3K14la‐mediated transcription of the ferroptosis‐related genes TFR and SLC40A1, indicating the role of lactate in regulating EC‐related pathogenesis of lung injury and providing a new therapeutic strategy for the treatment of sepsis‐associated ARDS. Here, TFRC is linked to acute respiratory distress syndrome.