Hypoxia is one of the most significant abiotic stresses affecting organisms in aquatic environments. However, dissolved oxygen in water is not always at the low concentrations that cause hypoxia, but their levels often fluctuate. Here, golden pompano (Trachinotus blochii) was subjected to low oxygen concentrations for 28 days (intermittent hypoxia, 2 h per day), and their metabolic indexes were systematically evaluated. RNA-seq was used to construct a regulatory network to elucidate the transcriptional regulation of golden pompano metabolism under intermittent hypoxia. We found that the liver lactic acid content, as well as hexokinase and phosphofructokinase activities, were elevated during the first 7 days, suggesting that anaerobic glycolysis was enhanced during the preceding period. In addition, triglyceride, lipoprotein lipase, and carnitine palmitoyltransferase-1 levels were elevated in the liver after 14 days, suggesting that lipid utilization was activated after 14 days. Intermittent hypoxia increased the activity of aspartate aminotransferase and alanine aminotransferase in the liver, decreased total plasma protein and amino acid levels, and enhanced the metabolism of proteins and amino acids. Decreased levels of oxidative stress and LOEcrit (the O