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Aquaculture supplies large quantities of high-value proteins to human beings and remains the most efficient protein-producing industry. Fish feed is the largest cost during aquaculture practice, and it is of great importance to explore the nutrient requirements and physiology of different aquatic animals. The last decade has seen a growing number of studies revealing the metabolic responses in aquatic animal nutrition, physiology and disease. The inner metabolic regulatory mechanism in aquatic animal nutrition, physiology and disease remains largely unresolved. This Special Issue Reprint showcases a collection of original research articles that highlight the latest discoveries and advances in the field of metabolic research in aquatic animal nutrition, physiology and disease. In improving our understanding of the metabolic regulation in multiple aspects of aquatic animals, there is potential to develop functional feed components or high-efficiency fish feed, to finally promote the continual blooming of the aquaculture industry.