We studied the features of acute enteral failure in patients with peritonitis in the setting of COVID-19 by studying the properties of the enteral pathobiome, biochemical, functional, pro-inflammatory and anti-apoptotic markers in diffuse peritonitis. A retrospective randomized cohort controlled study was conducted; it included 84 patients divided into two groups. Stratified randomization was used. The species composition and properties of the enteral luminal pathobiome were studied. 699 inoculations were made, resulting in 3024 isolates. The enteral morphofunctional coefficient, the level of alkaline phosphatase and its intestinal isoform were dynamically studied. In immunohistochemical studies, we studied the expression of CD-3 and Bcl-2. Patients with COVID-19 in addition to a decrease in the level of saprophytic microflora, showed a significant increase in Klebsiella spp., Candida, Clostridium spp. and Citrobacter (p≤0.05). The rate of antibiotic resistance in the comparison group was 8.3%, in the main group - 36.9%. MRSA pathogens were noted in 86.4% of cases, VRSA strains were found in 20.6% of cases. Patients with COVID-19 had a deficiency of intestinal alkaline phosphatase, which persisted even on the day 5 of treatment. Macro- and microscopic studies showed pronounced inflammatory and apoptotic changes in the intestinal wall of patients in the main group. A specific enteral pathobiome that is multiresistant to antibiotics, pronounced inflammatory and apoptotic changes in the intestinal wall, and a predisposition to perforation of the small intestine are characteristics of enteral failure in diffuse peritonitis in the setting of COVID-19.