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The prediction of the occurrence of infectious diseases is of crucial importance for public health, as clearly seen in the ongoing COVID-19 pandemic. Here, we analyze the relationship between the occurrence of a winter low-pressure weather regime - Cyprus Lows - and the seasonal Influenza in the Eastern Mediterranean. We find that the weekly occurrence of Cyprus Lows is significantly correlated with clinical seasonal Influenza in Israel in recent years (R = 0.91; p <.05). This result remains robust when considering a complementary analysis based on Google Trends data for Israel, the Palestinian Authority and Jordan. The weekly occurrence of Cyprus Lows precedes the onset and maximum of Influenza occurrence by about one to two weeks (R = 0.88; p <.05 for the maximum occurrence), and closely follows their timing in eight out of ten years (2008–2017). Since weather regimes such as Cyprus Lows are more robustly predicted in weather and climate models than individual climate variables, we conclude that the weather regime approach can be used to develop tools for estimating the compatibility of the transmission environment for Influenza occurrence in a warming world. Furthermore, this approach may be applied to other regions and climate sensitive diseases. This study is a new cross-border inter-disciplinary regional collaboration for appropriate adaptation to climate change in the Eastern Mediterranean. Unlabelled Image • The occurrence of Cyprus Lows and Influenza are significantly correlated over Israel, the Palestinian Authority and Jordan. • The occurrence of Cyprus Lows precedes the onset/maximum of Influenza incidence by 1-2 weeks and follows their timing. • This relationship can be used to develop tools to estimate the compatibility of the environment for Influenza occurrence. [ABSTRACT FROM AUTHOR]