SARS-CoV-2 pneumonia and COVID-19 disease are characterized by a maladaptive immune response and prothrombotic state. The Spike protein of SARS-CoV-2 virus unleashes a storm of lipid mediators with very high levels of thromboxane B2 and prostaglandin D2 in the bronchoalveolar lavage fluid. DPr2 receptors for prostaglandin D2 and TPr receptors for thromboxane A2 have been proposed as therapeutic targets in COVID-19 in order to decrease viral load and inhibit platelet dependent thrombosis, respectively. Ramatroban is an oral, dual receptor antagonist of the DPr2 and TPr receptors with established safety profile, having been used in Japan for the treatment of allergic rhinitis for over 20 years. We report two patients, an 88-year-old woman and a 31-year-old man, both with COVID-19 pneumonia who were successfully treated in ambulatory setting with oral ramatroban, leading to rapid improvement in oxygen saturation from about 80–82% to about 90–95% over 24–48 hours followed by gradual recovery from the disease. The mechanism of action of ramatroban and its efficacy reported here supports clinical trials on this drug as a potential treatment for COVID-19.