An analytical method based on pressurised liquid extraction (PLE) followed by liquid chromatography-high resolution mass spectrometry (Orbitrap) was developed for the simultaneous determination of ten high-intensity sweeteners in fish samples. As the method was developed, the different PLE parameters were optimised and different clean-up strategies were evaluated, of which in-cell clean-up using alumina and on-cell clean-up with hexane were the most effective. PLE recoveries were between 43% and 94%. The method quantification limits were between 12.5ngg−1 dry weight (d.w.) and 250ngg−1 (d.w.) and the method detection limits between 2.5ngg−1 (d.w.) and 125ngg−1 (d.w.). Intra-day precision and inter-day precision were below 16% and 25%, respectively. Fish samples from different species were analysed and, saccharin was found below its method quantification limit in the species Scomber scombrus (Atlantic mackerel).