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The multiple ecosystem services (ES) co-produced by social-ecological systems include ES directly resulting from ecosystem functioning, and ES mediated by human activities, which can have negative effects on the system and on the ES provided. As a result, different patterns of multiple ES delivery can be characterized by sustainable or unsustainable trends over time, depending on the interactions occurring among ES. In this paper, a sustainability perspective was used for the identification of desirable and undesirable ES delivery patterns in the water bodies of the Venice lagoon (Italy). A set of 13 ES was quantitatively mapped for the lagoon's water bodies, and the trends of the ES provided by each water body have been explored through a modeling application. Two aggregated indicators, MED/DIR and PRESS/DIR, calculated based on the mapping outcomes, were found to be strongly associated with the modeled trends, and thus provide a synthetic indication of the potential (un)sustainability of the current ES provision. This sustainability-driven analysis paves the way for an operationalization of the ES concept in the context of the implementation of the EU Water Framework Directive (2000/60/EC). Based on the analysis of the relationships between multiple ES and ecological status, we suggest that ES could play a role in the selection of the biological quality elements, by prioritizing the metrics that are positively associated with the sustainable ES patterns. Adopting a perspective focused on sustainability, the ES concept can be used to define management trajectories that aim to reach the WFD targets through the management of unsustainable ES patterns, in the context of climate change.