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Background and Aims: Ileus, mechanical bowel obstruction, and acute colonic pseudo-obstruction are characterized by distension of the intestines with accumulated bowel gas. Current treatments are not completely satisfactory. Methods: By manipulating the partial pressures of oxygen and nitrogen in the trapped air with a novel 6-hour treatment with 100% oxygen via nonrebreather mask, the bowel can be successfully decompressed, facilitating resolution of the underlying condition. Results: A positive clinical response was seen in 7/8 [87.5%] patients after therapeutic oxygen for gastrointestinal atony. Maximal lumen diameter decreased by an average of 1.14 ± 0.87 cm [16%]. Conclusion: In this first clinical report of therapeutic oxygen for gastrointestinal atony, the provision of 100% oxygen via nonrebreather mask is a useful therapy. It decreased the diameter of the intestinal lumen and enhanced resolution of ileus, acute colonic pseudo-obstruction, and bowel obstruction. This is a low-morbidity, low-cost treatment of gastrointestinal luminal distension.ClinicalTrials.gov Identifier NCT03386136.st.