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Assessing water supply sustainability is crucial to meet stakeholders' needs, notably in the Mediterranean. This region has been identified as a climate change hot spot, and as a region where water demand is continuously increasing due to population growth and the expansion of irrigated areas. The Hérault River catchment (2500 km2, France) is a typical example and a negative trend in discharge has been observed since the 1960s. In this context, local stakeholders need to evaluate possible future changes in water allocation capacity in the catchment, using climate change, dam management and water use scenarios. A modelling framework that was already calibrated and validated on this catchment over the last 50 years was used to assess whether water resources could meet water demands at the 2030 horizon for the domestic, agricultural and environmental sectors. Water supply sustainability was evaluated at the sub-basin scale according to priority allocations using a water supply capacity index, frequency of unsatisfactory years as well as the reliability, resilience and sustainability metrics. Water use projections were based on the evolution of population, per-unit water demand, irrigated areas, water supply network efficiency, as well as on the evaluation of a biological flow. Climate projections were based on an increase in temperature up to 2°C and a decrease in daily precipitation by 20%. Adaptation strategies considered reducing per-unit water demand for the domestic sector and the importation of water volume for the agricultural sector. The dissociated effects of water use and climatic constraints on water supply sustainability were evaluated. Results showed that the downstream portions would be the more impacted as they are the most exploited ones. In the domestic sector, sustainability indicators would be more degraded by climate change scenarios than water use constraints. In the agricultural sector the negative impact of water use scenarios would be stronger. The environmental sector would be hardly satisfied especially in summer with low resilience levels. The adaptation strategies considered in this study would not be sufficient to cope with both anthropogenic and climate changes. Other strategies were discussed based on known examples in the Mediterranean context., (Copyright © 2015 Elsevier B.V. All rights reserved.)