In the setting of septic challenge, the production of central HMGB1 has been identified as a major contributor to cognitive dysfunction, as HMGB1 antagonism significantly alleviated brain injury and offered improvement in neurological disorders, indicating that the enhanced production of HMGB1 should be noted and addressed with prompt interference to protect the central nervous system against severe sepsis [15, 21]. This evidence concerns the gene HMGB1 and Sepsis.