Background: We previously reported that severe COVID-19 patients had higher chances of survival and a reduced risk of developing respiratory failure when administered with the probiotic formulation SLAB51. This study aimed to investigate further bacteriotherapy mechanisms and how early they are activated. Methods: We performed an analysis on the blood oxygenation parameters collected in sixty-nine severe COVID-19 patients requiring non-invasive oxygen therapy and presenting a CT lung involvement ≥50%. Twenty-nine patients received low-molecular-weight heparin, azithromycin and Remdesivir. In addition, forty subjects received SLAB51. Blood gas analyses were performed before the beginning of treatments and at 24 h. Results: The patients receiving only standard therapy needed significantly increased oxygen amounts during the 24 h observation period. Furthermore, they presented lower blood levels of pO2, O2Hb and SaO2 than the group also supplemented with oral bacteriotherapy. In vitro data suggest that SLAB51 can reduce nitric oxide synthesis in intestinal cells. Conclusions: SARS-CoV-2 infected patients may present lesions in the lungs compromising their gas exchange capability. The functionality of the organs essential for these patients’ survival depends mainly on the levels of pO2, O2Hb and SaO2. SLAB51 contains enzymes that could reduce oxygen consumption in the intestine, making it available for the other organs.