Background <p>This study aims to evaluate the gastrointestinal implications of the Omicron variant, focusing on intestinal injury.</p> Methods <p>This retrospective, single-center study analyzed a case series of 12 Omicron patients with hemorrhagic colitis at the First Hospital of Yangtze University in December 2022.</p> Results <p>The study involved 12 Omicron patients with hemorrhagic colitis, aged 52 to 72 years. The primary clinical symptoms included abdominal pain and hematochezia. Laboratory findings in some patients showed decreased hemoglobin, elevated D-dimer, and increased C-reactive protein levels. Abdominal CT demonstrated intestinal wall thickening and exudation. Colonoscopy revealed intestinal damage characterized by varying degrees of erythema, erosion, and ulceration. The most common site of lesions was the sigmoid colon, followed by the transverse colon and descending colon. Histopathological examination revealed a decrease in the glands within the lamina propria of the intestinal mucosa, along with focal infiltration of neutrophils or lymphocytes and interstitial hemorrhage. Following the treatment, 11 patients improved significantly, while one patient died from multiple organ dysfunction syndrome (MODS), secondary to severe COVID-19 pneumonia.</p> Conclusion <p>The Omicron may be associated with intestinal injury. Most patients could recover after receiving conservative treatment.</p>