Deep hypothermic cardiopulmonary bypass (CPB) is used in selected procedures such as pulmonary endarterectomy (PEA) and aortic arch repair. Hypothermia induces metabolic and physicochemical changes that affect hydrogen ion concentration ([H⁺]), haemoglobin–dioxygen (O₂) binding, O₂ consumption, and carbon dioxide (CO₂) production. Modern blood gas analysers provide instantaneous measurements of blood pH, PO₂, and PCO₂, enabling rapid bedside assessment of acid–base disturbances. Accurate interpretation, however, requires an understanding of the underlying physical and chemical principles. Acid–base management during hypothermic CPB is typically guided by either a pH-stat (interpreting blood gases at the patient’s actual temperature) or an alpha-stat strategy (interpreting blood gases at 37°C, independently of the patient’s actual temperature). The optimal strategy remains debated. This review clarifies key physiological principles of acid–base regulation, the effects of temperature on blood pH and gas solubility, and their clinical implications, with the aim of supporting accurate interpretation of blood gas values during hypothermic CPB.