AbstractThe novel coronavirus disease (COVID-19) still remains a major challenge to the health-care systems worldwide, inciting ongoing search for pharmaceutical and non-pharmaceutical interventions which could benefit patients already infected with SARS-CoV-2 or at increased risk thereof. Although SARS-CoV-2 primarily affects the respiratory system, it may also infect other organs and systems, including gastrointestinal tract, where it results in microbial dysbiosis. There is an emerging understanding of the role the gut microbiota plays in maintaining immune homeostasis, both inside the gastrointestinal tract and beyond (i.e. through gut–lung and gut–brain axes). One family of compounds with recognized immunomodulatory and anti-inflammatory properties are short chain fatty acids (SCFAs). SCFAs are believed that they have a protective effect in case of gastrointestinal diseases. Moreover, they are responsible for maintaining proper intestinal barrier and they take part in relevant immune functions. This review presents mechanisms of action and potential benefits of SCFA-based probiotics and direct SCFA supplementation as a strategy to support immune function amid the COVID-19 pandemic.