Abstract: Dysregulated inflammation and multi-organ failure are hallmarks of sepsis, a potentially fatal illness for which there are currently no effective treatments. Fatty acid-binding protein (A-FABP) has been identified in recent research as a crucial mediator of the inflammatory pathways underlying sepsis. In this study, we used a murine model of lipopolysaccharide (LPS)-induced endotoxemia to assess the therapeutic potential of 6H2, a monoclonal antibody that targets A-FABP. In comparison to untreated septic mice, 6H2 treatment significantly increased survival rates, decreased histopathological damage in the liver, lungs, kidneys, and heart, and reduced systemic inflammation. According to biochemical analyses, 6H2 treatment decreased circulating levels of A-FABP, and this was associated with a reduction in inflammatory markers. These results indicate that A-FABP inhibition is a potentially effective treatment approach for sepsis, with 6H2 demonstrating strong therapeutic efficacy.