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The study assesses the direct effects of climate change by 2060, including extreme events, on the productivity of regional crop farming and livestock in Greece, and the broader socio-economic effects on the agri-food and other sectors. Different approaches (i.e., agronomic models, statistical regression models, and equations linking thermal stress to livestock output) were combined to estimate the effects on productivity from changes in the average values of climatic parameters, and subsequently the direct economic effects from this long-term climate change. Recorded damages from extreme events together with climatic thresholds per event and crop were combined to estimate the direct economic effects of these extremes. The broader socio-economic effects were then estimated through input–output analysis. Under average levels of future extreme events, the total direct economic losses for Greek agriculture due to climate change will be significant, from EUR 437 million/year to EUR 1 billion/year. These losses approximately double when indirect effects on other sectors using agricultural products as inputs (e.g., food and beverage, hotels, and restaurants) are considered, and escalate further under a tenfold impact of extreme events. Losses in the GDP and employment are moderate at the national level, but significant in regions where the contribution of agriculture is high. [ABSTRACT FROM AUTHOR]