Background: Spontaneous bacterial peritonitis (SBP) is the most frequent bacterial infection in patients who suffer from liver cirrhosis and ascites. Prostaglandin E2 (PGDE2) is considered a simple and accurate tool for diagnosing systemic inflammation and has a relevant impact on prognosis in cirrhotic patients. Objective: We tried to detect the role of PGDE2 in serum and ascitic fluid as a diagnostic marker for eradication of SBP. Patients and methods: This clinical-based prospective cohort study involved patients with liver cirrhosis, ascites and spontaneous bacterial peritonitis referred to the Internal Medicine Department, Faculty of Medicine, Zagazig University during the period from June 2020 to March2021. Patients with ascites were divided equally into: (a) case group included cirrhotic patients with SBP); and (b) control group included cirrhotic patients without SBP. All patients were subjected to complete clinical and laboratory examination. Serum and ascitic PGDE2 were estimated before and after five days of treatment. Results: There was statistically significant difference between the studied groups regarding Child score and presence of HCC. Serum and ascitic PGDE2 was elevated in all cirrhotic groups; both of case and control had more than normal. However, PGDE2 level was lower in case group before treatment in comparison with control group, and after treatment PGDE2 levels was elevated. Conclusion: Serum and ascitic fluid PGDE2 can be used as a diagnostic marker for SBP diagnosis and eradication. Serum PGDE2 is preferred due to its less invasiveness and minimal risk of complications.