A 53-year-old man was admitted for respiratory failure due to severe acute respiratory syndrome caused by a severe acute respiratory syndrome coronavirus 2 infection. The patient required prolonged artificial ventilation and extracorporeal membrane oxygenation (ECMO) for respiratory support. Despite successful discontinuation of ECMO, the patient experienced profuse watery diarrhea (5-10 L/day). A colonoscopy revealed an inflamed surface without undulation that uniformly extended throughout the colon. Biopsy specimens revealed complete disappearance of existing crypts and replacement with squamous or transitional epithelium normally observed in the anal transitional zone mucosa, with granulation tissue proliferation in the lamina propria. Watery diarrhea persisted despite corticosteroid and infliximab administration. Although diarrhea due to atrophy of the surface and cryptic epithelium as an intestinal manifestation of coronavirus disease 2019 usually responds to corticosteroids, refractory diarrhea can be attributed to squamous metaplasia with complete disappearance of the surface and cryptic epithelium.