This chapter provides a comprehensive overview of the metabolic derangements that occur during cardiopulmonary bypass (CPB) procedures. CPB, a critical component in many cardiac surgeries, involves diverting blood away from the heart and lungs, allowing for surgical interventions on a still heart. While lifesaving, this process can lead to significant metabolic disturbances due to the altered physiological state. This chapter focuses on the complex metabolic and electrolyte changes encountered during CPB in cardiac surgery. It emphasizes the alterations in oxygen delivery and consumption, glucose metabolism, and electrolyte disturbances, primarily driven by the unique conditions of CPB. Key aspects include the interplay between oxygen transport mechanisms and CPB pump flow, as well as the management of metabolic acidosis and tissue oxygen demands, highlighted by discussions on serum lactate levels and acid–base balance. Notably, this chapter sets the stage for more detailed explorations of related topics in other chapters of the book. These include the physiological and metabolic implications of therapeutic hypothermia, the challenges and strategies of hemodilution, comprehensive acid–base management during CPB, and the complexities of drug pharmacokinetics in the CPB setting. By providing a focused overview of these critical aspects, the chapter serves as a foundational guide for understanding the broader metabolic challenges in CPB, paving the way for deeper insights into associated topics in later chapters. This approach ensures a cohesive and comprehensive understanding of the metabolic management in cardiac surgery, crucial for optimizing patient outcomes.