Overfishing not only drastically reduces the number of fish in an exploited populationbut is also often selective for body size by removing the largest individuals from apopulation. Here, we study experimentally the evolutionary effects of size-selectiveharvesting using whole-genome sequencing on a model organism, the zebrafish(Danio rerio). We demonstrate genomic shifts in the populations exposed to size-selective harvesting for five generations and show reduced genetic diversity in allharvested lines, including the control line (non-size-selected). We also determine dif-ferences in groups of genes related to certain gene ontology annotations betweensize-selectively harvested lines, with enrichment in nervous system related genes inthe large-selected lines. Our results illuminate the biological processes underlyingfisheries-induced genetic changes and hence contribute toward the understanding ofthe changes potentially associated with the vulnerability of an exploited populationto future stressors.