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Background & Aims: The use of non-selective beta-blockers has been associated with lower rates of infection and reduced infection-associated morbidity in patients with cirrhosis. However, it is unknown if these drugs modify the systemic inflammatory response to circulating bacterial DNA., Methods: Sixty-three patients with cirrhosis were included during an episode of decompensation by ascites. Thirty of those patients were on beta-blockers. Blood samples were obtained after each patient had been in the supine position for at least 30 minutes in a quiet atmosphere. Bacterial DNA, serum cytokines, nitric oxide, and LPS were determined. Phagocytic and oxidative burst activities were determined in polymorphonuclear cells from the patients., Results: The detection rate of bacterial DNA in the blood was the same (33%) for patients not treated and treated with non-selective beta-blockers. Patients naive to non-selective beta-blockers showed significantly higher serum levels of IL6, IFN-gamma and IL10 in response to the presence of bacterial DNA. Patients treated with non-selective beta-blockers showed higher basal inflammatory activity that did not change with the presence of bacterial DNA. Monocytes and granulocytes from patients treated with non-selective beta-blockers showed a significantly increased phagocytic capacity in the presence of bacterial DNA., Conclusions: In patients with cirrhosis, chronic treatment with beta-blockers is associated with a higher unstimulated production of serum cytokines and an increased phagocytic activity in the presence of bacterial DNA., (© 2018 The Authors Liver International Published by John Wiley & Sons Ltd.)