Background Spontaneous bacterial peritonitis (SBP) is one of the most critical complications in chronic liver disease patients with ascites. Lipocalin 2 (Lcn2), also known as neutrophil gelatinase associated lipocalin (NGAL), is a 25 kDa protein present in peroxidase negative granules of neutrophils, and is released following neutrophil activation. Lipocalin 2 is a promising marker for diagnosis of infections, especially in chronic liver diseases (CLD). Objective This study aims to evaluate role of serum and ascitic lipocalin-2 as a reliable biomarker in diagnosis of SBP and as a predictor of short term in-hospital mortality in patients with chronic liver disease -related SBP. Methods This case-cohort study was conducted on 80 patients with CLD &Ascites, 40 patients with SBP infections and 40 patients without SBP . All patients were subjected to measurement of lipocalin-2 levels in both serum and ascitic fluids by enzyme-linked immune-sorbent assay (ELISA) kits . For SBP cases , Siderophores production was determined among bacterial isolates quantitatively by modified CAS assay method and analyzed genetically by multiplex polymerase chain reaction (PCR) ,then cases were followed up for 30 days in hospital mortality. Results The results indicated that ascites Lipocalin-2 was significantly higher in patients with SBP compared to those without SBP. In ROC analysis, ascites Lipocalin-2 had an AUC of 0.845 as a marker for diagnosis of SBP cases . Sixteen (40%) patients died in the hospital. In the final multivariate model, MELD score, Creatinine , INR, Total and direct bilirubin remain significant predictors of in-hospital mortality (P<0.05). Conclusion Ascitic fluid Lipocalin-2 level can be used as a diagnostic marker of SBP in hospitalized patients with cirrhosis with high sensitivity and specificity, especially in chronic liver disease patients . MELD score remains an independent predictor of short-term survival in-hospital mortality .