Both <i>in vitro</i> and <i>in vivo</i> experiments showed that silencing UBE2F markedly suppressed dendritic cell activation, decreased proinflammatory cytokine production and organ injury, and ultimately improved survival in septic mice.<h4>Conclusions</h4>Our results reveal cDC1 as a key immune cell subset involved in ubiquitination-mediated immune dysregulation in sepsis and suggests that UBE2F may serve as a potential diagnostic biomarker and therapeutic target. This evidence concerns the gene UBE2F and Sepsis.