The Mediterranean countries are anticipated to face considerable warming and drying with uncertain precipitation patterns further exacerbating the vulnerability of semi-arid regions, like Sardinia. Sardinia’s vineyards, crucial to the local economy and cultural heritage, are increasingly threatened by climate change risks, particularly affecting physiological processes, which can compromise grapeyields and wine quality. The research aims to assess the impact of climate change on evapotranspiration demand in Sardinian vineyards, while keeping into account mitigating effects (e.g. reduced stomatal conductance) due to atmospheric CO2concentration increase. This study utilizes the Simulation of Evapotranspiration of Applied Water (SIMETAW_GIS) model to evaluate the impact of climate change on water demand of vineyards in Sardinia region, Italy. The research leverages high-resolution climate future projections to evaluate how varying climate conditions will affect the water demand of vineyardsunder three Representative Concentration Pathways (RCP2.6; RCP4.5; RCP8.5). Additionally, the analysis addresses the uncertainty associated with rising atmospheric CO2 concentration, evaluating both the direct impact of CO2 fertilization and without these effects. Increasing CO2 can improve water use efficiency, partially mitigating negative impacts following rising temperatures and uncertain precipitation patterns. The results revealed that grapevine water demand is projected to rise by 5%-7% withCO2fert and 7%-10% withCO2constreflecting a relative percentage change between the historical period (1976-2005) and mid-century (2036-2065) under future projection (RCP2.6; RCP4.5; RCP8.5). The inclusion of CO2 effects significantly alters canopy resistance in the reference evapotranspiration (ET0) estimation, thus limiting vegetation water demand. The research highlights the importance of integrating the CO2 effects into crop water demand assessment and underscores the necessity for adaptive irrigation strategies to the resilience and sustainability of Sardinian vineyards amidst rapidly evolving climate conditions.