Background and Objectives: The COVID-19 pandemic has had a profound impact on societies worldwide, prompting preventive measures to mitigate its effects. Among the critical issues in managing COVID-19 patients is improving oxygenation and SATURATION status. In this study, we investigated the efficacy of inhaled H2O8 administered via a nebulizer for patients in the moderate to severe inflammatory phase of COVID-19. Methods: We conducted a case-control study involving COVID-19 patients with moderate to severe pulmonary involvement admitted to the intensive care unit (ICU) between October 2021 and March 2022. Using simple random sampling, we selected 120 patients from two hospitals. These patients were divided into two groups: the intervention group received H2O8 liquid via nebulization every half hour, while the placebo group received normal saline through the same device. Results: The study recorded the proportion of males and the mean age of patients in both the treatment and placebo groups. Specifically, in the treatment group, 60. 0% were male (36 patients) with a mean age of 70. 5±13. 2 years. In the placebo group, 71. 7% were male (43 patients) with a mean age of 73. 2±11. 6 years. The P values for these comparisons were 0. 178 and 0. 233, respectively, indicating no significant differences. Additionally, no significant differences were observed based on other underlying variables between the two groups. However, when it came to SpO2 levels, there was a notable finding. Five minutes after consumption, the average SpO2 in the treatment group (H2O8) was significantly higher than in the placebo group (89. 2±4. 2 vs. 83. 4±5. 2, P < 0. 001). Two hours later, the mean SpO2 remained higher in the treatment group (85. 5±4. 3) compared to the placebo group (83. 7±5. 2), although this difference did not reach statistical significance at the 10% level (P = 0. 056). Furthermore, the study revealed that patients in the treatment group had a significantly shorter hospital stay compared to those in the placebo group (8. 4±2. 2 days vs. 9. 8±2. 0 days, P = 0. 001). Interestingly, after two hours, there was no significant statistical difference in the baseline sections, but this difference became significant at the 5% level after five minutes. Conclusion: Our findings suggest that nebulized H2O8 effectively treats moderate and severe pulmonary COVID-19 cases. This strategy not only reduces ICU hospitalization duration but also mitigates inflammation factors compared to current therapies.