AbstractWe investigate hydrodynamic cavitation to inactivate commonly employed Saccharomyces cerevisiae yeast strains in an aqueous solution using different reactors and hydraulic circuit selected to demonstrate the process feasibility on the industrial scale. The target to achieve an useful lethality of the yeast at lower temperature when compared with standard thermal and even with other cavitation processes was achieved, with 90% yeast strains lethality at lower temperature (6.3–9.5°C), and about 20% lower energy input. A separate model simulating the combined thermal and cavitational effects on yeast lethality allows to accommodate the data into a comprehensive framework providing a tool to design further targeted experiments and to predict results when changing the process parameters.