COVID-19 has affected over 110 million patients worldwide till February 2021. Scientists seek to understand the pathophysiology and proposed several theories. COVID-19 severe clinical phenomena occurred due to cytokine storms that cause hypochlorous acid (HOCl) production. HOCl has several harmful effects on hemoglobin, like heme degradation and iron overload toxicity. There are two theories about the attack of COVID-19 on Hemoglobin. One widely shared hypothesis based on the docking model, recommended that SARS-CoV-2 proteins ORF1ab and ORF3a bind to hemoglobin protein, changing heme to ORF10, resulting in the breakdown of the heme into iron and Protoporphyrin IX (PPIX), causing the loss of hemoglobin function and iron toxicity. Objection theory depends on comparing the experimental analysis between patients with COVID-19 and acute respiratory distress syndrome (ARDS) patients. The results showed that COVID-19 patients were not showing any hemolytic anemia or altering the hemoglobin-oxygen dissociation curve and hence, COVID-19 has no role in the removal of iron and oxygen delivery. In addition, there is a hypothesis that hemoglobin structure plays a role in the physiopathology of COVID- 19 disease. In children a high fetal hemoglobin levels leading to a decrease in the mortality rate with COVID-19. Another hypothesis linked between the blood grouping and the risk of developing COVID-19 infection.  O group persons have a lower chance for infection. From all the previous studies, many drugs formulated like fetal hemoglobin inducers, Iron chelators, and Lactoferrin represents options for the treatment of COVID-19. The present review is an attempt to describe some hypothesizes related to the Hemoglobin theory. I n addition to information about some new therapies used in the treatment of COVID-19.