It is well documented that antibiotics have pronounced modulatory effects on the intestinal bacterial community of both humans and animals, with potential health consequences. The gut microbiota of mink has however attracted little attention due to low bacterial load and fast gastrointestinal transit time, questioning its relevance. In this study, we hypothesise that oral amoxicillin treatment affects the gut microbiota in mink. This was investigated in a controlled trial including 24 animals of which 12 were treated with amoxicillin for 7 days. By applying 16S rRNA gene sequencing, we found that the faecal microbiota was markedly altered already after 2 days of treatment, with a surprising increase in diversity to resemble the feed. The diversity within the mucosa at termination was however reduced, which indicates this compartment as an important colonisation site in mink. No impact on blood biochemistry, lipid metabolism, serum amyloid A, vitamins A and E and histomorphology of the gut and liver was found; however, a slight decrease in fat digestibility was observed. We suggest that early-life use of amoxicillin in mink production may be counteractive as dysbiosis of the microbiota during infancy is increasingly being recognised as a risk factor for future health.