Background: The historically recent domestication of fishes has been essential for mankind due to the overexploitation of natural stocks and the increasing protein demand to meet the needs of a growing human population. Selection for relevant traits, such as growth, during domestication is a complex process whose epigenetic basis is poorly understood. Results: We have determined changes that occur in the muscle transcriptome after a single generation of Nile tilapia (Oreochromis niloticus) domestication. There was a downregulation of 2015 genes in fish reared in captivity compared to their wild progenitors. In contrast, several myogenic and metabolic genes that can affect growth potential were upregulated. Methods: RNA was extracted and ribosomal RNA was removed using the Ribo-Zero gold rRNA removal kit. RNA libraries were prepared using the NEBNext Ultra II directional RNA library prep kit for Illumina. In total, we obtained 480 million 150 bp paired-end reads. Conclusion: Taken together, our data indicate that thousands of genes were differentially expressed within a single generation of fish domestication. Overall design: Fast muscle RNA-Seq from rRNA depleted libraries of 5-month old Wild type (W) and first generation of fish undergoing domestication (D) females in six replicates. W and D samples are genetically paired (i.e., each D sample corresponded to a W progenitor) and at the same ontogeny stage. The pairs are grouped according to their numbers (i.e. W53 - D53, W63 - D63)