Salinity fluctuations constitute a well-known high stress factor strongly shaping global biological distributions and abundances. However, there is a knowledge gap regarding how increasing saline stress affects microbial biological interactions. We applied the combination of a probabilistic method for estimating significant co-occurrences/exclusions and a conceptual framework for filtering out associations potentially linked to environmental and/or spatial factors, in a series of connected ephemeral (hyper) saline lakes. We carried out a network analysis over the full aquatic microbiome –bacteria, eukarya and archaea– under severe salinity fluctuations. Most of the observed co-occurrences/exclusions were potentially explained by environmental niche and/or dispersal limitation. Co-occurrences assigned to potential biological interactions remained stable, suggesting that the salt gradient was not promoting interspecific facilitation processes. Conversely, co-exclusions assigned to potential biological interactions decreased along the gradient both in number and network complexity, pointing to a decrease of interspecies competition as salinity increased. Overall, higher saline stress reduced microbial co– exclusions while co–occurrences remained stable suggesting decreasing competition coupled with lack of stress-gradient promoted facilitation in the microbiome of ephemeral saline lakes.