Lepidonotothen nudifrons, a notothenioid fish belonging to the family Nototheniidae (red-blood species), is endemic to the Southern ocean. It is benthic and moderately active. L. nudifrons is expecially abundant along the western Antarctic Peninsula where it plays an ecologically important role as prey to piscivorous fish species (Llompart et al. 2014 and references therein). In this study we characterized for the first time a spleen-specific transcriptome in an Antarctic notothenioid (L. nudifrons) obtained by Illumina sequencing of paired-end normalized library of spleen RNA (cDNA). The data obtained disclosed a broad catalogue of genes expressed in spleen tissue of L. nudifrons, which are involved in several intracellular immune signalling pathways. Future investigations will target the possible correlation between thermal sensitivity and immune response.