Cellular immune depression is linked to high mortality in sepsis, but has yet to be systematically analysed in liver cirrhosis. The aim of the present study was to directly compare functional immune parameters in patients with acute on chronic liver failure (ACLF), severe sepsis, and non-decompensated cirrhosis. Patients with ACLF (n=27) were investigated at admission to a medical ICU. Patients with stable liver cirrhosis (n=24) and severe sepsis (n=31) served as control groups. In all subjects, serum levels of IL-6 and IL-10, ex vivo production of TNF-αin a whole blood assay, and monocyte surface HLA-DR expression were determined. In patients with ACLF or sepsis, ex vivo TNF-αproduction and HLA-DR expression were severely decreased compared to subjects with stable cirrhosis (both P< 0.001). Contrary, IL-6 levels were highest in septic patients, followed by subjects with ACLF and cirrhotic patients (both P< 0.05). Immune dysfunction in ACLF was independent of aetiology of liver cirrhosis and associated with high mortality. Patients with ACLF and severe sepsis show a similar degree of cellular immune depression. The reduced cellular immune function in subjects with ACLF might contribute to the increased infectious morbidity of these patients and provide a rational basis for prevention strategies. Cellular immune depression is linked to high mortality in sepsis, but has to be systematically analyzed in liver cirrhosis. The aim of the present study was to directly compare functional immune parameters in patients with acute on chronic liver failure (ACLF), severe sepsis, Patients with ACLF (n = 27) were investigated at admission to a medical ICU. Patients with stable liver cirrhosis (n = 24) and severe sepsis (n = 31) served as control groups. In all subjects, serum levels of IL-6 and IL-10, ex vivo production of TNF-αin a whole blood assay, and monocyte surface HLA-DR expression were determined. In patients with ACLF or sepsis, ex vivo TNF-α production and HLA-DR expression were severely decreased compared to subjects with stable cirrhosis (both P <0.001). Contrary, IL-6 levels were highest in septic patients, followed by subjects with ACLF and cirrhotic patients (both P <0.05). aetiology of liver cirrh Patients with ACLF and severe sepsis show a similar degree of cellular immune depression. The reduced cellular immune function in subjects with ACLF may contribute to the rational infectious disease of these patients and provide a rational basis for prevention strategies.