The consequences of antibiotic use in aquatic integrated systems, which are based on trophic interactions between different cultured organisms and physical continuity through water, need to be examined. In this study, fish reared in a prototype marine integrated system were given an oxolinic acid treatment, during and after which the level of resistance to this quinolone antibiotic was monitored among vibrio populations from the digestive tracts of treated fish, co-cultured bivalves and sediments that were isolated on thiosulfate–citrate–bile–sucrose. Oxolinic acid minimum inhibitory concentration distributions obtained from replica plating of thiosulfate–citrate–bile–sucrose plates indicated that a selection towards oxolinic acid resistance had occurred in the intestines of fish under treatment. In contrast, and despite oxolinic acid concentrations higher than minimum inhibitory concentrations of susceptible bacteria, no clear evolution of resistance levels was detected either in bivalves or in sediments.