While several studies point at off-shore aquaculture as a possible source of impacts on the local marine environment, very few have analysed its effects at large scales such as at the bay, gulf or basin levels. Similar analyses are hampered by the multiple sources of disturbance that may concomitantly affect a given area. The present paper addresses these issues taking the Gulf of Castellammare (Southern Tyrrhenian Sea) as an example. Nitrogen (N) and phosphorous (P) loads were calculated for the period 1970-2007, and compared to chlorophyll-a concentration as measured inside and outside the Gulf over the same period. Results indicate that N and P catchment loading has constantly decreased because of improved environmental management. Nevertheless, nutrient concentration in the Gulf has steadily increased since the establishment of aquaculture facilities in 1999. Chlorophyll-a concentration followed this trend, showing a marked increase from 2001 onwards. In the same period, chlorophyll-a concentrations measured inside and outside the Gulf have significantly diverged. As all the other possible causes can be ruled out, aquaculture remains the sole explanation for the observed situation. This paper demonstrates for the first time ever that off-shore aquaculture may affect the marine ecosystem well beyond the local scale and provides an additional element of concern to be kept into consideration when allocating oceans' space for new fish-farming activities.