Oxysterols have emerged as important bioactive lipids in the immune response to infectious diseases. This chapter discusses our current knowledge of oxysterols and their receptors in bacterial and viral infections of the respiratory and gastrointestinal tracts. Oxysterols are produced in response to infections and have multiple roles including chemotaxis of immune cells to the site of infection and regulation of inflammation. Some oxysterols have been shown to possess antiviral or antibacterial activity.Lastly, we delve into the emerging mechanisms of action of oxysterols. Oxysterols can enhance host cell resistance via reduction of membrane accessible cholesterol, modulate membrane immune signalling, and impact inflammasome activation and efferocytosis.