The number of hospitalizations and fatalities brought on by COVID-19 has considerably grown since the World Health Organization proclaimed the disease as a global pandemic. New combination therapy is required to lessen the risk of COVID-19 progression during this time when the danger of transmission rises as new Omicron sub-variants arise. In this situation, it is critical to boost the immune system to combat highly inflammatory conditions like the cytokine storm brought on by COVID-19. Furthermore, if administered early in COVID-19 illness, monoclonal antibodies (mAbs) that neutralize SARS-CoV-2 can minimize the chance of hospitalization. LY-CoV1404 (bebtelovimab) is one of these mAbs that has recently gained prominence due to its ability to effectively neutralize the SARS-CoV-2 virus and protect binding to spike proteins of several variants including B.1.1.529 (Omicron) and its subvariants (BA.1, BA.1.1, and BA.2) with various essential receptor binding domain (RBD) mutations. This brief review emphasizes the advantages of combining melatonin with bebtelovimab, which has been demonstrated to be the most effective SARS-CoV-2 neutralizing monoclonal antibody against the Omicron variant in the management of COVID-19. This study suggests that the combination therapy for Omicron sub-variants is beneficial and could be regarded as adjuvant therapy for COVID-19 disease.