Defoliation is an indicator for forest health in response to several stressors including air pollutants, and one of the most important parameters monitored in the International Cooperative Programme on Assessment and Monitoring of Air Pollution Effects on Forests (ICP Forests). The study aims to estimate crown defoliation in 2030, under three climate and one nitrogen deposition scenarios, based on evaluation of the most important factors (meteorological, nitrogen deposition and chemical soil parameters) affecting defoliation of twelve European tree species. The combination of favourable climate and nitrogen fertilization in the more adaptive species induces a generalized decrease of defoliation. On the other hand, severe climate change and drought are main causes of increase in defoliation in Quercus ilex and Fagus sylvatica, especially in Mediterranean area. Our results provide information on regional distribution of future defoliation, an important knowledge for identifying policies to counteract negative impacts of climate change and air pollution.