The relationship between the gut microbiome and various organ systems has gained interest throughout the scientific community in recent times. The understanding of these complex relationships has greatly improved with clinical benefits now being seen. Cardiopulmonary bypass (CPB) is a form of extracorporeal circulation that provides circulatory and respiratory support during cardiac surgery. This physiological support facilitates a still and bloodless field facilitating operations on the heart to be performed. Through various mechanisms CPB results in a systemic inflammatory response syndrome (SIRS). This response can vary from mild hypotension to multiple organ failure. It remains difficult to predict the degree to which a patient will experience SIRS post-operatively. The relationship between the composition of the gut microbiome and inflammatory processes associated with disease has been seen across several fields including gastroenterology, neurology, psychiatry and cardiology. To date, minimal research has been undertaken to examine the impact the gut microbiome has on outcomes following cardiac surgery. This review paper explores the pathophysiology behind the SIRS response associated with CPB for cardiac surgery and the hypothesis that a correlation exists between a patients gut microbiome composition and the degree of inflammatory response experienced following cardiac surgery.