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Mediterranean coastal lagoons are particularly vulnerable to increasing direct anthropogenic threats and climate change. Understanding their potential responses to global and local changes is essential to develop management strategies adapted to these ecosystems. Salinity is a fundamental structuring factor for phytoplankton communities; however, its role under climate change is understudied. We hypothesized that salinity variations imposed by climate change and/or management actions could disturb Mediterranean lagoons’ phytoplankton communities. To test our hypothesis, we performed two 5-day microcosm experiments in which natural phytoplankton assemblages from the Santa Giulia lagoon (Corsica Island) were subjected to three increasing (53–63–73) and decreasing (33–26–20) levels of salinity, to mimic strong evaporation and flash flooding, respectively. Results indicate that over-salinization inhibited growth and modified the assemblages’ composition. Freshening, on the contrary, showed feeble effects, mainly boosting microphytoplankton abundance and depleting diversity at lowest salinity. In both experiments and under freshening in particular, initially rare species emerged, while photosynthetic activity was degraded by salinity increase only. We demonstrated that phytoplankton communities’ structure and metabolism are strongly altered by the predicted implications of climate change. Such impacts have to be considered for future management of coastal lagoons (control of sea exchanges and watershed fluxes). This work constitutes a priority step towards the proactive adapted management and conservation of such as-yet-neglected ecosystems in the context of climate change.