Purpose: To investigate the role of fi-eudesmol in septic liver injury in mice. Methods: Mice were intraperitoneally injected with 50 or 100 mg/kg fi-eudesmol, and then subjected to cecal ligation and puncture for the establishment of a septic model 2 h later. Haematoxylin and eosin staining was used to evaluate histopathological changes in the liver tissues. Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) staining and enzyme-linked immunosorbent assay (ELISA) were employed to determine liver damage, while inflammation and oxidative stress were evaluated by ELISA. Results: Liver tissues of septic mice showed infiltration of inflammatory cells, vacuolar degeneration and obscure nucleus. However, treatment with fi-eudesmol ameliorated the histopathological changes (p < 0.01). Moreover, fi-eudesmol also reduced hepatocyte apoptosis, and decreased the levels of biomarkers for liver damage. The up-regulation of TNF-a, IL-1fi, IL-6 in septic mice were significantly down-regulated by fi-eudesmol (p < 0.01), but increased the levels of superoxide dismutase (SOD) and glutathione (GSH) and decreased malondialdehyde (MDA) and myeloperoxidase (MPO) in order to protect the mice against sepsis. In addition, fi-eudesmol attenuated the cecal ligation and puncture-induced up-regulation of p-p65 in mice (p < 0.01). Conclusion: fi-Eudesmol exerts anti-inflammatory and anti-oxidant effects in septic mice by inactivating NF-KB signaling, and thus may be useful as a potential agent in the management of sepsis.