Background: The intestinal microbiota of certain farmed fish is often exposed to antimicrobial substances, such as antibiotics, that are used to prevent and treat bacterial diseases. Antibiotic treatment, which is intended to kill or inhibit the growth of harmful microorganisms, can rapidly alter the intestinal microbial diversity and composition, with potential effects on the host health. In this study, we have elucidated the effects of two antibiotics, florfenicol and oxolinic acid on the distal and mid intestinal microbial communities of Atlantic salmon (Salmo salar). We employed high-throughput 16S rRNA gene amplicon sequencing to investigate the bacterial communities in the intestinal mucus of Atlantic salmon fed diets with and without antibiotics. Results: Our results show that antibiotic exposure shifts the intestinal microbial profile differentially. Beta diversity analysis revealed significant differences between the bacterial compositions of the control and antibiotic-fed groups. Antibiotic-feeding altered the composition and abundance of the dominant bacterial phyla viz. Proteobacteria, Actinobacteria, Firmicutes, Spirochaetes, Bacteroidetes, Tenericutes, and Thermotogae. Furthermore, the bacterial association network analysis revealed that the co-occurrence pattern of bacteria of the three study groups were different. Conclusion: We conclude that both florfenicol and oxolinic acid can modulate the composition and interaction of the intestinal microbiota of Atlantic salmon. This knowledge will be helpful in future studies, investigating the prevalence of antibiotic-resistant intestinal bacteria in farmed salmon and the economic impact of modulating the gut microbiota of salmon via antibiotic feeding.