Solar proton events (SPEs) affect the Earth’s atmosphere, causing additional ionization in the high-latitude mesosphere and stratosphere. Ionization rates from such solar proton events maximize in the stratosphere, but the formation of ozone-depleting nitrogen and hydrogen oxides begins at mesospheric altitudes. The destruction of mesospheric ozone is associated with protons with energies of about 10 MeV and higher and will strongly depend on the intensity of the flux of these particles. Most studies investigating the impact of SPEs on the characteristics of the middle atmosphere have been based on either simulations or reanalysis datasets, and some studies have used satellite observations to validate model results. We study the impact of SPEs on cold-season ozone loss in both the northern and southern hemispheres using Aura MLS mesospheric ozone measurements over the 2004 to 2024 period. Here, we show how strongly SPEs can deplete polar mesospheric ozone in different hemispheres and attempt to evaluate this dependence on the intensity of solar proton events. We found that moderate SPEs consisting of protons with an energy of more than 10 MeV and a flux intensity of more than 100 pfu destroy mesospheric ozone in the northern hemisphere up to 47% and in the southern hemisphere up to 33%. For both hemispheres, the peak of winter ozone loss was observed at about 76 km. In the northern hemisphere, maximum winter ozone loss was observed on the second day after a solar proton event, but in the southern hemisphere, winter ozone depletion was already detected on the first day. In the southern hemisphere, mesospheric ozone concentrations return to pre-event levels on the ninth day after a solar proton event, but in the northern hemisphere, even on the tenth day after a solar proton event, the mesospheric ozone layer may not be fully recovered. The strong SPEs with a proton flux intensity of more than 1000 pfu lead to a maximum winter ozone loss of up to 85% in the northern hemisphere, and in the southern hemisphere winter, ozone loss reaches 73%.