We have investigated the impact of a large mussel farm on the benthic environment using a battery of benthic indicators of environmental quality (including biochemical, microbial and meiofaunal parameters). These were analysed through a multi-control sampling strategy over one year. The differences across the seasons are typically higher than those between the impacted and the control stations. No effects are seen in terms of the sediment oxygen penetration and the downward fluxes (as the total mass, organic and phytopigment fluxes). The indicators based on the biochemical compositions of the sediment organic matter and the microbial parameters also show no evidence of the eutrophication process, except as a slight increase in the bacterial density in the sediments beneath the long-lines of the farm during the period of highest mussel stocks. Finally, no effects are observed in terms of the benthic faunal indicators, as the meiofaunal abundance, the community structure and the taxa richness are all indistinguishable between the farm sediments and the controls. These results show that mussel farming in the investigated system is eco-sustainable and does not significantly alter the coastal marine ecosystem, both in terms of the functioning and the trophic state. The battery of indicators selected in this study represents a useful tool for the monitoring of the potential ecological impact of mussel farms, towards guaranteeing the sustainable development of aquacultures in shallow coastal environments.