The impacts of Persistent Organic Pollutants (POPs) are assessed in fat tissue (blubber) using live explant samples from young grey seals (Halichoerus grypus) on the east coast of Scotland. The data show POP levels in blubber and responses to intrinsic pollutants and experimental exposure to polychlorinated biphenyls (PCBs), relevant due to its applicability to other species, including humans. The study sites are located on the Isle of May (56° 10’ 58.79” N, 02° 32’ 57.56” W) between October and December 2015, 2016, and 2017, where the grey seal population had been monitored annually and from where previous POP data from blubber tissue was investigated in 2002. A second sample set was collected from yearling grey seals hauled out on the Isle of May, Moray Firth, and Culbin Sands (57° 39’10” N, 03° 43’ 15” W) and maintained in temporary captivity at the Sea Mammal Research Unit between February and August 2018. The capture and explant data includes animal identifier, moulting state (where relevant for yearlings), whether the animal was fed or fasted (where relevant for pups), body and sample tissue mass. Characteristics of the animals like sex, birth, and weaning date (where known), rate of mass change, life history stage and blubber fat content, including intrinsic blubber POP levels, were measured at the Centre for Analytical Research and Technology at the University of Liège, Belgium to be used as covariates in a Generalised Additive Mixed Model (GAMM). This analysis was undertaken after accelerated solvent extraction of the samples in hexane dichloromethane (Dionex 200 by Thermo Fisher Scientific) and the extracts were analysed using a gas chromatograph (Agilent 6890 GC) coupled to Autospec Ultima High-Res Mass Spectrometer. The response of explants was tested through measurement of gene expression (using the Stratagene Mx3000P qPCR System or StepOne Plus Real-Time PCR System), insulin signaling and glucose uptake, lactate production, oxygen consumption and lipolytic rate using Randox Monza assays. Thyroid hormones triiodothyronine (TT3) and thyroxine (TT4) were measured using Enzyme Linked Immunosorbent Assays (ELISA Fortress Diagnostics Ltd). The live explants were treated overnight with a mix of PCBs and organochlorine pesticide derivatives (DDT, DDE), which were associated with altered metabolic function symptoms such as glucose uptake and lactate production in 2015-2017. The data will facilitate an understanding of the molecular mechanisms of contaminant-induced disruption of energy balance by legacy pollutants in seals during their most vulnerable life stages. The data collection was led by Dr Kimberley Bennett from Abertay University and funded by the NERC Discovery Science project “Obesogens in a naturally obese animal: An experimental approach to assess the impact of marine pollutants on fat tissue function in seals”, parent grant reference NE/M013723/1 with child grant NE/M01357X/1.