AIMS: Coronavirus disease 2019 (COVID-19) has been recognized as a predominantly respiratory tract infection, but some patients manifest severe systemic symptoms/coagulation abnormalities. We evaluated the impact of severe COVID-19 infection on the gastrointestinal tract. METHODS AND RESULTS: We examined clinicopathologic findings in 28 resected ischemic bowels from 22 patients with severe COVID-19. Most patients required intubation preoperatively and presented with acute decompensation shortly before surgery. D-dimer levels were markedly elevated in all measured cases (mean: 5394 ng/mL). Histologically, 25 cases (19 patients) showed evidence of acute ischemia with necrosis. In this group, the most characteristic finding was the presence of small vessel fibrin thrombi (24/25 cases, 96%), which were numerous in 64% of cases. Compared to a control cohort of 35 non-COVID-19-related acute ischemic bowels, patients with COVID-19 were significantly more likely to show isolated small intestine involvement (32% vs. 6%, p<0.001), small vessel fibrin thrombi (100% vs. 43%, p<0.001), submucosal vessels with fibrinous degeneration and perivascular neutrophils (90% vs. 54%, p<0.001), fibrin strands within submucosal vessels (58% vs. 20%, p=0.007), and histologic evidence of pneumatosis (74% vs. 34%, p=0.010). Three cases in this cohort had histopathologic findings normally seen in the setting of chronic ischemia, notably prominent fibroblastic proliferation affecting the outer layer of the muscularis propria. CONCLUSIONS: Herein, we describe the histopathologic findings in COVID-19-associated ischemic bowel and postulate a relationship to the hypercoagulable state seen in patients with severe COVID-19 infection. Additional experience with these cases may further elucidate specific features or mechanisms of COVID-19-associated ischemic enterocolitis.