Fecal calprotectin is considered a valid marker of intestinal inflammation and its high level in patients with HE may be explained by small intestinal bacterial overgrowth. This study aimed to assess the role of fecal calprotectin in diagnosis and follow up of patients with hepatic encephalopathy. Fifteen patients with uncomplicated liver cirrhosis, 30 patients with liver cirrhosis complicated by hepatic encephalopathy (HE) and 15 healthy subjects were enrolled. All participants were subjected to: clinical examination, laboratory investigations (CBC, liver function tests, kidney functions, HBs Ag and HCV Antibody), fecal calprotectin concentration, abdominal ultrasound. Severity of HE was assessed according to West–Haven criteria. Patients with HE was managed using metronidazole and rifaximin and fecal calprotectin concentrations were reassessed. The level of fecal calprotectin is significantly higher in patients with Child-Pugh class B (116±12 mg/kg) versus that in class A (66±15 mg/kg) (p<0.01). FC concentrations showed the lowest value in the cirrhotic group (66+15 mg/kg) followed by low grade HE (195+12mg/kg) and the highest value in the high grade HE group (489+23mg/kg) (p<0.01). A significant decrease in FC concentrations occurred in HE group after receiving treatment, reaching a level of 273+42.68 mg/kg versus 364+83.12 mg/kg before rifaximin. In conclusion: Fecal calprotectin can be used in diagnosis of HE. Significant high levels of fecal calprotectin in high grade HE patients and its reduction following effective treatment could consider fecal calprotectin as a follow up marker in association with clinical signs in patients with HE.