Leopard coral grouper (Plectropomus leopardus) is one of the most important cultured fish in Pacific and Indian oceans. Vibrio harveyi is a serious pathogen causing serious skin ulceration and high mortality in P. leopardus. To gain more insight into the tissue-specific and dynamic immune regulation process of P. leopardus in response to V. harveyi infection, RNA-seq was used to examine the transcriptome profiles in spleen and liver at 0, 6, 12, 24, 48 and 72 h post-infection (hpi).