Vaucluse is a department in the southeastern French region of Provence-Alpes-Côte d'Azur. It had a population of 561,469 as of 2019. The de…Vaucluse is a department in the southeastern French region of Provence-Alpes-Côte d'Azur. It had a population of 561,469 as of 2019. The department's prefecture is Avignon. It is named after a spring, the Fontaine de Vaucluse, one of the largest karst springs in the world. The name Vaucluse itself derives from the Latin Vallis Clausa as the valley ends in a cliff face from which the spring emanates.