Scientific researchers recently showed that endocannabinoid system is involved in the management of infectious agents such as viruses, bacteria, and some protozoa, also reducing inflammation and pain in the lungs [74]. In view of the fact that SARS-CoV-2 infection leads to increase the pro-inflammatory cytokines, including IL-6 and IL-1β in COVID-19 patients via binding to the TLRs, an important components of the innate immune system, it is assumed that OEA inhibits this pathway through its anti-inflammatory properties [75]. OEA binds with high affinity to PPAR-α receptors and increases the expression level of anti-inflammatory cytokine such as IL-10, then initiates a cascade of events, which can attenuate the inflammatory responses [73]. Furthermore, OEA attenuates the inflammatory responses modulating the expression of TLR-4, and interfering with the ERK1/2/AP-1/STAT3 signaling cascade [73]. OEA may modulate cross-talk between PPAR-α and TLRs and regulates the inflammatory responses with beneficial synergistic effect against SARS-CoV-2. Nowadays, discovering therapeutic options from currently available agents appears to be essential for the treatment and prophylaxis of this pandemic, especially in obese patients with comorbidities [76] and this bioactive lipid mediator can be considered as a novel potential pharmacological alternative for the management of COVID-19.