The major pathogen associated with eggs is Salmonella enterica subsp. enterica serovar Enteritidis (S. Enteritidis) and chlorine washing is the most widely used for sanitization. Microbubble, a novel technique and able to operate in large quantity, has been presented to be an alternative method. Thus, microbubble water combining with ozone (OMB) was applied to disinfect S. Enteritidis spiked on shells at 107 cells per egg. OMB was generated by injecting ozone into a Nikuni microbubble system, then delivered into 10 L of water. After 5, 10, or 20 min of activation time, the eggs were placed into OMB and washed for 30 or 60 s. The controls involved unwashed, water washing, ozone only, and microbubble only (MB). The highest reduction, 5.19 log CFU/egg, was achieved by the combination of 20-min activation and 60-s washing, which was used for following tests of large water quantities. Comparing with the unwashed control, 4.32, 3.73 and 3.07 log CFU/egg reductions were achieved in 25, 80, and 100 L of water, respectively. The other system, Calpeda, with higher motor power was tested in 100 L and obtained a reduction of 4.15 log CFU/egg. The average diameter of bubbles generated by Nikuni and Calpeda pump systems were 29.05 and 36.50 μm, respectively, which both were within the microbubble definition of ISO. Much lower reductions, around 1–2 log10 CFU/egg, were shown with the treatments of ozone only and MB by the same operative parameters. After 15-day storage at ambient temperature, the OMB-treated eggs showed similar sensory quality with the unwashed ones. This is the first study demonstrating that OMB effectively inactivates S. Enteritidis on shell eggs in large quantity of water and does not diminished the sensory characteristics of eggs. Furthermore, bacterial population was under the detection limit in the OMB-treated water.