In this study, we describe a de novo sequencing and assembly of the spleen transcriptome of Lepidonotothen nudifrons, a notothenioid fish widely distributed around the Antarctic Peninsula and the Scotia Arc. Sequences were generated on an Illumina MiSeq system and assembled to a total of 112,477 transcripts. Putative functional annotation was possible for more than 34% of the transcripts. This data will be relevant for future studies targeting the erythrocyte turnover, oxygen transport mechanism and immune system, which are key functional traits to investigate cold adaptation and thermal sensitivity of Antarctic notothenioids.