The gut microbiome is an integral component of fish health and growth performance and therefore represents an important production factor in aquaculture. Antibiotics are a major stressor, not only by disturbing microbial diversity, but also by altering microbial interactions involved in digestion, colonization resistance and functional redundancy. Current risk assessments, however, rely largely on diversity-based evaluations and rarely consider changes in network topology. Here, we investigated the impact of florfenicol on the gut microbiome of Nile tilapia (Oreochromis niloticus) using 16S rRNA sequencing, combining conventional diversity metrics with microbial co-occurrence network modelling. While the microbial community remained overall stable at the diversity level, with treatment explaining only a minor proportion of the observed variation, network analysis revealed substantial fragmentation and a less robust network structure. Network connectivity was significantly reduced, with a near-complete turnover of central hub taxa in the florfenicol network. Our findings demonstrate that diversity-based assessments alone may substantially underestimate the extent of antibiotic-induced microbiome disturbance, with network analysis capturing changes within the community that are highly relevant for microbiome stability and would otherwise remain undetected when evaluations are restricted to diversity metrics.