The aim of this paper is to review the factors which may affect breath ¹³CO2/¹²CO2 natural abundance in patients undergoing surgery or intensive care. Intravenous glucose administration is a major determinant of the ¹³CO2/ ¹²CO2 of breath as intravenous glucose preparations are almost all derived from cornstarch. In addition, the oxidation of endogenous substrates can affect the ¹³CO2/¹²CO 2 ratio. During many endoscopic procedures, such as laparoscopic surgery, carbon dioxide insufflation is used to provide a working space. As medical CO2 is relatively depleted in ¹³CO2 compared with endogenous and exogenous metabolic CO2 sources, breath ¹³CO2/¹²CO2 measurements can be used to estimate CO2 absorption during these procedures. However, all these factors may also be affected by the bicarbonate pool, making a definitive attribution of changes in breath ¹³CO2/ ¹²CO2 to a single factor problematic.