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Abstract BackgroundPerfluoroalkyl substances (PFAS) are persistent environmental contaminants previously used for industrial purposes as a non‐stick coating and flame retardant. The stability of these molecules prevents their breakdown, which results in ground water contamination across the globe. Perfluoroalkyl substances molecules are known to bioaccumulate in various organisms. However, the health consequences remain unclear due to the large number of molecules in the PFAS family and different effects on various tissues. Here, we use the frogXenopus laevisto investigate the developmental consequences of exposure to the PFAS molecule perfluoro‐octanoic sulfonate (PFOS). ResultsWe find that exposure to high levels of PFOS results in significant axial shortening of developing tadpoles. Further, we find that PFOS exposure results in a dose‐dependent formation of a cellular mass in the dorsal fin. Unexpectedly, we found that these developmental phenotypes are exacerbated upon co‐exposure with commonly used antibiotics. Specifically, PFOS and gentamicin co‐treatment results in increased apoptosis, loss of cellular integrity, and increased overall lethality. ConclusionsOur results suggest a mechanism whereby gentamicin reaches levels that are toxic to mitochondria only in the presence of PFOS. These findings add to our understanding of PFOS exposure to vertebrate development and present an added concern with potential interactions with antibiotics.