Microplastic pollution is a growing environmental issue, even reaching remote areas like the Arctic and Antarctic, posing threats to biodiversity and food chains. The present research represents a pioneering endeavor aimed at exploring the relationship between lipids and microplastics in 20 wild specimens of Trematomus bernacchii from the Ross Sea (Antarctica). Fish were grouped in MPs-ingested and MPs-free based on whether they had ingested microplastics. Raman spectroscopy revealed that contaminated fish samples contained from one to three different types of polymeric fibers (1.4 items/specimen, ± = 0.7), specifically, polyester (PES), polypropylene (PP), and polyethylene terephthalate (PET). Gas chromatography-mass spectrometry (GC–MS) and gas chromatography-flame ionization detection (GC-FID) techniques were employed for the study of the lipid composition in term of fatty acids methyl esters (FAMEs). Fifty different FAME compounds were identified and quantified in the lipid fraction extracted from the muscle tissues of the selected fish samples. Polyunsaturated fatty acids (PUFAs) are the most abundant family of fatty acids in T. bernacchii species with eicosapentaenoic (C20:5ω3) and docosahexaenoic (C22:6ω3) acids as main components. In detail, PUFA class accounted for 46.78 ± 6.82% and 44.62 ± 4.86% of the total fatty acid composition in MPs-ingested and MPs-free groups, respectively. The contents of the monounsaturated fatty acids (MUFAs) and saturated fatty acids (SFAs) varied from 27.93% to 31.15% and from 24.23% to 25.05% in MPs-ingested and MPs-free fish samples, respectively. Based on Mann-Whitney test results (p < 0.05), there was no significant difference from a statistical point of view between two groups of fishes. Additionally, nutritional quality indices exhibited comparable values between groups. Results showed that no significant differences were found in the fatty acids distribution between the two groups. This indicates that the lipid composition of wild fish that are naturally exposed to plastic pollution remains unchanged and could still have beneficial effects on human health.