Clinical analysis revealed that elevated <i>Blautia</i> abundance in sepsis patients inversely correlated with pulmonary injury severity and positively associated with augmented CD8<sup>+</sup> T cell effector functions.<h4>Discussion</h4>Our findings establish that <i>Blautia</i> and <i>Blautia</i>-derived IAA mitigates SI-ALI by counteracting CD8<sup>+</sup> T cell depletion and dysfunction, highlighting a novel and promising mechanism-based therapeutic strategy for life-threatening sepsis. Here, CD8A is linked to acute respiratory distress syndrome.