Bacterial infections impair prognosis in patients with cirrhosis. Presepsin and, more recently, resistin are promising markers of infection and sepsis in patients without cirrhosis. The aim of our study was to assess the performance of presepsin and resistin as early markers of infection compared with C reactive protein (CRP) and procalcitonin (PCT), and their prognostic relevance in patients with decompensated cirrhosis. One hundred and fourteen consecutive patients with decompensated cirrhosis were enrolled and followed-up for 28 days. Diagnostic performances of CRP, PCT, presepsin and resistin were assessed. Fifty-three (46.5%) patients had bacterial infections of which 30 (56%) had sepsis. Presepsin and resistin had similar performance as CRP and PCT for the diagnosis of infection (best cut-off of 1444 pg/ml and 20 ng/ml, respectively) and sepsis. Presepsin (HR = 5.5; 95%CI: 2.36–13.21, p < 0.0001) and the ≥500 pg/ml increase of presepsin at 48 h (HR = 9.24; 95%CI: 3.66–23.27, p < 0.008) were independently associated with 28-day mortality. Presepsin and resistin have similar diagnostic performances to CRP and PCT for bacterial infection in decompensated cirrhosis. Presepsin and Δ presepsin ≥500 pg/ml have also a prognostic relevance for 28-day mortality.