The emergence of the novel coronavirus SARS-CoV-2, which causes severe respiratory tract infections in humans (COVID-19), has become a global health concern. One of the most worrying features of COVID-19 is a phenomenon known as the “cytokine storm”, which is a rapid overreaction of the immune system. Additionally, coagulation abnormalities, thrombocytopenia and digestive symptoms, including anorexia, vomiting, and diarrhea, are often observed in critically ill patients with COVID-19. Baker’s yeast β-glucan, a natural immunomodulatory component derived from Saccharomyces cerevisiae, primes the immune system to respond better to any microbial infection. Our previous studies have shown that oral administration of yeast β-glucans decreased the diarrhoea, modulated cytokine expression, and reduced the intestinal inflammation. Additionally, we showed that β-glucan fractions decreased coagulation in plasma and reduced the activation of platelets. During the period of home confinement facing individuals during the COVID-19 pandemic, our immune defence could be weakened by different factors, including stress, anxiety and poor nutrition, while a healthy diet rich in vitamins C and D can reinforce the immune defence and reduce the risk of microbial infections. Additionally, β-glucan can be used to strengthen the immune defence in healthy individuals prior to any possible viral infections. This short review focuses on the role of baker’s yeast β-glucan, with a healthy diet rich in natural vitamins C and D, in addition to a healthy gut microbiota can provide synergistic immune system support, helping the body to naturally defend prior to respiratory virus infections, until stronger options such as vaccines are available.