Sepsis represents a life-threatening condition that frequently accompanies acute hepatic dysfunction. As a result of systemic inflammation, immune dysregulation, and microcirculatory derangements, different types of liver dysfunction can occur, such as hypoxic hepatitis, sepsis-associated cholestasis, or liver failure. A very serious and late sequela is secondary sclerosing cholangitis of the critically ill patient. Clinical management of sepsis-related liver dysfunction includes the rapid identification and treatment of the suspected underlying infection, hemodynamic stabilization to improve hepatic perfusion, and the optimization of oxygen delivery to the liver. Despite maximum efforts in supportive treatment, the outcome of patients with sepsis or septic shock and concomitant severe hepatic dysfunction remains very poor.