We aimed to investigate the protective effects of S-adenosylmethionine (SAMe) and silybin treatment on hepatorenal and hemostatic functions in dogs with endotoxemia. Healthy dogs (n = 20) were divided equally into 4 groups as control, SAMe + silybin (SS), lipopolysaccharide (LPS), and LPS + SS. Controls received 0.9% NaCl intravenously. Animals were treated daily with 20 mg of SAMe and 1 mg of silybin per kilogram of body weight in SS and LPS + SS. LPS was injected (2 mu g/kg, once intravenously) to dogs in LPS and LPS + SS. Hemostatic functions were assessed by thromboelastography (TEG). LPS-induced clinical and hematological changes were attenuated (P < 0.05) by SS treatment. Serum blood urea nitrogen and creatinine increased at 1-24 h (P < 0.05) after LPS. They did not changed in LPS + SS. LPS associated increases in liver enzymes were inhibited at 1-24 h in LPS + SS. In TEG, reaction time, coagulation time, and a-angle, but not maximum amplitude and G values, were significantly changed after LPS. These responses were restored by SS treatment in dogs with LPS. SS administration may be beneficial by regulating coagulation and protecting hepatorenal function in dogs with endotoxemia.