The sea cucumber Apostichopus japonicus is a deposit-feeder and vital for marine benthic ecosystems. Hypoxia lasting for several days can lead to massive mortality in A. japonicus. It is important to understand the molecular responses of A. japonicus when exposed to acute changes in DO concentration. In the present study, RNA-seq provided a general overview of the gene expression profiles of the respiratory tree of A. japonicus exposed to dissolved oxygen (DO) of 8 mg/L (DO8), 4 mg/L (DO4) and 2 mg/L (DO2) conditions. Overall design: One group of sea cucumbers was maintained as the control group with high DO water (DO8) at around 8 mg/L, whereas the other two groups were kept in sea water with nitrogen aeration where the DO concentration gradually decreased to approximately 4 mg/L DO (DO4) and 2 mg/L DO (DO2), which is defined as hypoxia, and they were maintained for 3 days.