The increasing global demand for cheap, available protein has resulted in substandard animal feeds which generally lack essential minerals and often contain toxic levels of heavy metals. Cd is a bio-toxic heavy metal and exposure causes DNA strand breakage, mutations and inhibition of DNA synthesis. Selenium (Se) is an essential trace element that possesses antioxidant properties. In this study, the potential ameliorative effects of various Se sources on Cd induced damage were investigated. The impact of several forms of Se supplementation on cell viability and DNA damage in porcine primary jejeunal (IPEC-J2) cells following Cd exposure was analysed. It was observed that Se protective effects were both composition- and dose-dependent, with organic (Se-M) and Se yeast (Se-Y) affording the highest level of protection from Cd-induced oxidized DNA damage while inorganic Se exhibited cytotoxic effects. The potential mechanism(s) of action of Se-Y sources on Cd-induced damage were then compared. Thus, the antioxidant activity, the extent of apoptosis-associated DNA fragmentation, the DNA repair capacity and the transcriptome of IPEC-J2 cells were analysed following pre-incubation with each of three different commercial Se-Y preparations. The data obtained confirmed the ability of different Se-Y preparations to enhance a range of cellular mechanisms that protected IPEC-J2 cells and clearly illustrated the difference in bioefficiency of different Se-Y sources. Overall, the results presented are relevant to the Agri-Food industry, illustrating the negative impact of traditional inorganic Se supplementation and highlighting the significant benefits to using Se-Y in animal feed products for the protection of intestinal cells against Cd induced oxidative DNA damage.