Antibiotics play a vital role in aquaculture where they are commonly used to treat bacterial dis-eases. However, the impact of antibiotic treatment on the gut microbiome and development of an-timicrobial resistance in Nile tilapia (Oreochromis niloticus) over time, remains to be fully under-stood. In this study, fish were fed a single treatment of oxytetracycline (100 mg kg bodyweight-1) for eight days, followed by a 14-day withdrawal period. Changes in the distal gut microbiome were measured using 16S rRNA sequencing. In addition, the abundance of antimicrobial re-sistance genes was quantified using real-time qPCR methods. Overall, the gut microbiome com-munity diversity and structure of Nile tilapia was resilient to oxytetracycline treatment. Howev-er, antibiotic treatment was associated with an enrichment in Plesiomonas, accompanied by a de-cline in other bacteria taxa. Oxytetracycline treatment increased the proportion of tetA in the dis-tal gut of fish and tank biofilms in the OTC-group. Furthermore, the abundance of tetA along with other tetracycline resistance genes was strongly correlated with a number of microbiome mem-bers, including Plesiomonas. Findings from this study demonstrate that antibiotic treatment can exert selective pressures on the gut microbiome of fish, in favour of resistant populations which may have long-term impacts on fish health.