An understanding of the mechanistic drivers of microbial communities requires the incorporation of manipulative experiments, including manipulation of the existing microbes. As part of an ongoing study of the mechanisms that drive microbial communities in coral reef fishes, we tested the effects of the commonly used antibiotics Enrofloxacin and Nitrofurazone on three ornamental reef fish species: the four-eyed butterflyfish, Chaetodon capistratus (Chaetodontidae), the neon goby Elacatinus oceanops (Gobiidae), and the beaugregory damselfish Stegastes leucostictus (Pomacentridae). We bathed the fish in antibiotic (or no exposure in the controls), sampled the skin microbiota via swabbing at 0 (before treatment) and 3 and 7 days while in the treatments, and examined the microbial community using a small subunit ribosomal RNA gene sequencing approach. Our results showed that Nitrofurazone reduced skin-associated microbial diversity in all species and that the same effect for Enrofloxacin was only seen in S. leucostictus, compared to controls. While each antibiotic had its own, unique community impact, all treatments showed a shift in the most abundant microbial taxa over time. Moreover, both antibiotics increased the abundance of opportunistic or potential pathogens, such as Alteromonas and Vibrio. While both antibiotics are effective, Nitrofurazone more successfully reduces microbial diversity, and therefore may be more ideal for experiments seeking to disrupt normal fish microbiomes.