Air pollution is one of the main causes of damages to human health in Europe, with an estimate of about 380 000 premature eaths per year in the EU28, as the result of exposure to fine particulate matter (PM2:5) only. In this work, we focus on one specific region in Europe, the Po basin, a region where chemical regimes are the most complex, showing important non-linear processes, especially those related to interactions between NOx and NH3. We analyse the sensitivity of PM2:5 concentration to NOx and NH3 emissions by means of a set of EMEP model simulations performed with different levels of emission reductions, from 25% up to a total switch-off of those emissions. Both single and combined precursor reduction scenarios are applied to determine the most efficient emission reduction strategies and quantify the interactions between NOx and NH3 emission reductions. The results confirmed the peculiarity of secondary PM2:5 formation in the Po basin, characterised by contrasting chemical regimes within distances of a few (hundred) kilometres, as well as non-linear responses to emission reductions during wintertime. One of the striking results is the slight increase in the PM2:5 concentration levels when NOx emission reductions are applied in NOx -rich areas, such as the surroundings of Bergamo. The increased oxidative capacity of the atmosphere is the cause of the increase in PM2:5 induced by a reduction in NOx emission. This process could have contributed to the absence of a significant PM2:5 concentration decrease during the COVID-19 lockdowns in many European cities. It is important to account for this process when designing air quality plans, since it could well lead to transitionary increases in PM2:5 at some locations in winter as NOx emission reduction measures are gradually implemented. While PM2:5 chemical regimes, determined by the relative importance of the NOx vs. NH3 responses to emission reductions, show large variations seasonally and spatially, they are not very sensitive to moderate (up to 50 %–60 %) emission reductions. Beyond 25% emission reduction strength, responses of PM2.5 concentrations to NOx emission reductions become non-linear in certain areas of the Po basin mainly during wintertime.