Carfentanil is a synthetic opioid restricted to veterinary use due to its potency. Public health concerns have been raised as to the potential of carfentanil to exhibit toxicity after absorption via the percutaneous route following unintentional contamination. The current study measured the penetration of free base carfentanil through human, pig and rat skin using in vitro static diffusion cells. The human penetration rates were compared against literature toxicology values and indicated that, dependent on the contamination density, contamination area and residence time, skin decontamination and medical countermeasures may be required to ameliorate toxicity. The pig and rat skin penetration data will form the basis of future work to develop relevant in silico and in vivo models to further elucidate likely toxic effects and the medical strategies to mitigate against them.