Introduction In our manuscript we explore the impact of different anthropogenic stressors, namely mussel farming, methane extraction platforms and summer mass tourism, on the epipelagic microbiomes of the North-Western Adriatic Sea. Methods By 16S rRNA gene sequencing, we provided the epipelagic microbiome layout from selected sites corresponding to each of the considered impacts. As unimpacted reference, 16S rRNA sequencing data from Scicchitano et al. (2022) have been used. Results According to our findings, each one of the anthropogenic stressors resulted in a peculiar increase of specific epipelagic microbial components, also including potentially harmful pathogenic species. Discussion Besides providing evidence supporting the existence of recognizable and impact-driven fingerprint on the epipelagic marine microbiome peculiar for the different anthropogenic stressors, our findings also rise the concern of the ecological relevance of the observed changes, not only in terms of possible loss of ecosystem services, but also for the potential release of pathogenic microorganisms in the environment.