Background and rationale:  Spontaneous bacterial peritonitis (SBP) stands as a primary complication and the most common bacterial infection in individuals suffering from decompensated liver cirrhosis. It is linked to substantial morbidity and mortality rates. The study aimed to determine the level of MCP-1 gene expression in the ascitic fluid of liver cirrhotic patients with or without SBP to evaluate its role in SBP diagnosis and to evaluate the role of ascitic fluid (AF) calprotectin as a diagnostic biomarker for SBP in liver cirrhosis (LC) patients. Methods: A cross-sectional hospital-based study was conducted at Internal Medicine, Gastroenterology and Hepatology Unit at AL-Rajhi Hospital in the period between 2020 and 2022. Participants were divided into two groups, a SBP group (n = 37) and a non-SBP group (LC patients with ascites only) (n = 48). AF levels of MCP-1, calprotectin and blood chemistry tests were estimated in all patients. Results: Both studied groups had no significant differences as regards demographic and laboratory data, except lower potassium levels among the SBP group. Monocyte chemoattractant protein-1 (MCP-1) was significantly higher among the SBP group (p= 0.000) compared to the non-SBP group. Also, both groups had significant differences as regards calprotectin (p= 0.01). Only three patients in the SBP group had positive ascitic fluid cultures (Escherichia coli, Klebsiella pneumonia, and Acinetobacter baumannii) while the non-SBP groups were negative for bacterial growth. Only in the control group, did MCP-1 have a positive correlation with serum albumin and total bilirubin. Conclusion: Ascitic fluid MCP-1 and calprotectin are considered promising biomarkers for early diagnosis of SBP.