Listeria monocytogenes is a Gram positive ubiquitous psychrotrophic bacterium responsible for foodborne infections worldwide. L. monocytogenes is capable of growing at refrigeration temperatures in high salt and acid foods. In this study a response surface methodology was used to determine the effects and interactions of pH (4 to 10), temperature (4 ºC to 40 ºC) and ozonation time (5 seconds to 60 seconds) on the inactivation of L. monocytogenes strains ATCC 19115. The models were validated on Phosphate buffered saline inoculated with L. monocytogenes (108CFU/mL) using a batch reactor. According to the study, the optimum pH and the temperature for the total inactivation of L. monocytogenes falls in the range of 4.5-7.5 and 4˚C-15˚C respectively. Analysis of Variance showed that the coefficient determination value (R2) of L. monocytogenes inactivation was 0.9429. The study concluded that a 7 log reduction of L. monocytogenes can be successfully achieved by ozone exposure between 33 seconds and 49 seconds.