Antarctica is the continent with the lowest local human impact; however, it is susceptible to pollution from external sources. Emerging pollutants such as perfluoroalkyl substances pose an increasing threat to this environment and therefore require more in-depth investigations to understand their environmental fate and biological impacts. The present study focuses on expression analysis at the transcriptional level of genes coding for four antioxidant enzymes (sod1, sod2, gpx1, and gpx4) in the liver and kidney of an Antarctic fish species, Trematomus newnesi (Boulenger, 1902). mRNA levels were also assessed in fish exposed to 1.5 μg/L of perfluoro-octanoic acid for 10 days. The kidney showed a higher level of expression than the liver in wildlife specimens. In the liver, the treatment induced an increase in gene expression for all the considered enzymes, whereas in the kidney, it induced a general decrease. The obtained results advance the scientific community’s understanding of how the potential future presence of anthropogenic contaminants in the Southern Ocean can affect the antioxidant system of Antarctic fishes. The presence of pollutants belonging to the perfluoroalkyl substances in the Southern Ocean needs to be continuously monitored in parallel with this type of research.