In this study we evaluate whether the pattern of spatial variability of the macro-epiphytes assemblages of leaves of differed in relation to anthropogenic interference in the Gulf of Gabes (southern coast of Tunisia). A hierarchical sampling design was used to compare epiphytic assemblages at 5m depth in terms of abundance and spatial variability at disturbed and control locations. The results indicate that the biomass and mean percentage cover decreased at locations near the point of sewage outlet in comparison to control locations. These losses were related to the distance from the source of disturbance. This study revealed that the diversity is reduced in disturbed locations by the loss of biomass and the mean percentage cover, explained by means of a multiple-stressor model which plays an important role in the macro-epiphytes setting. It is urgent to propose the best management plans to save the remaining meadow in the Gulf of Gabes and its associated epiphytes.