A sharp reduction of the energy consumption of a high-speed centrifuge was obtained following several design changes, while still maintaining separation capacity. This reduction is necessary for making some applications commercially interesting, e.g., large-volume flow rates in the growing biopharma industry. The reduction was achieved by modifying flow paths of the rotor, i.e., reducing the outlet radius to minimize angular momentum losses and lowering the pressure drop of the internal flow. Further, removing air outside the rotor reduced aerodynamic losses, and using a direct drive motor, losses encountered with gear or belt drives were eliminated. This way, an average energy reduction of 50 % was obtained.