Introduction: Remdesivir (Veklury), a viral ribonucleic acid (RNA)-dependent RNA polymerase inhibitor designed by Gilead Sciences, has shown reductions in recovery time for coronavirus disease 2019 (COVID-19) patients, although its efficacy remains controversial. It has been proposed that combining remdesivir with immunomodulators may improve clinical efficacy. Mesenchymal stem cells (MSCs) exert immunomodulatory properties, which resolve COVID-19-induced pneumonia in early-phase trials. Menstrual blood-derived stem cells (MenSCs) present a novel MSC source, superior in availability, proliferative ability, and ethicality than traditional stem cell sources. This study aims to investigate the efficacy of remdesivir-MenSC combination therapy in resolving severe COVID-19-induced pneumonia. Methods: A randomized, double-blind, controlled study will be performed to assess two primary endpoints: time of recovery, defined as no longer requiring ongoing medical care, and normalization of the immune system, defined as the change in the concentration of key cytokines from baseline. Safety will also be measured as the frequency of treatmentrelated adverse events (AE). The study will aim to recruit 400 eligible subjects, aged 18 to 75, hospitalized with severe COVID-19, and they will be assigned to either receive intravenous (IV) infusions of MenSCs and remdesivir, or receive only remdesivir. A stratified log-rank test will be conducted to compare the time of recovery between study arms, with stratification by disease severity (baseline ordinal score). Two-way repeated measures ANOVA will be used to compare cytokine levels over time in the treatment group compared to the control group. Discussion: We expect remdesivir-MenSC combination therapy to surpass remdesivir in clinical efficacy and safety profile by improving clinical status, lowering duration of hospitalization, reducing mortality, and lowering the incidence of treatment-related AEs. Conclusion: Investigating this promising approach is an essential step in determining the feasibility of stem cell-based treatments in improving current COVID-19 therapeutics and patient outcomes. In particular, evaluating the clinical potential of MenSCs may provide insight into future therapeutic research as the literature has shown that MenSCs are superior to traditional MSC sources.