This study was conducted to determine the effect of fasting on body composition, muscle fatty acid profiles and biochemical parameters of serum in large yellow croaker (Larimichthys crocea). 105 net-cage cultured healthy fish with similar body weight (249.07±7.28 g) were selected for fasting experiment. The muscle and blood were sampled from experimental fish after 0, 3, 7, 14, 21, 28, 35, 42, 49 days of fasting for chemical analysis, respectively. The results showed that moisture and crude ash of muscle increased and crude fat decreased during fasting period. The protein content of muscle significantly decreased at 21 days of fasting and then remained constant. Saturated fatty acid (SFA) and monounsaturated fatty acid (MUFA) content in muscle showed no significant change(P>0.05), while the total polyunsaturated fatty acid (PUFA) and n-3 high unsaturated fatty acid (n-3HUFA) content significantly decreased at the end of experiment. The activities of serum alanine transaminase (ALT), glutamic-oxaloacetic transaminase (AST), lactate dehydrogenase (LDH) and the contents of serum glucose (GLU), Kalium (K⁺), sodium (Na⁺), calcium (Ca²⁺) and chloride (Cl^-) significantly increased, while serum triglyceride (TG), Cholesterol (CHOL) contents significantly reduced after 3 days of fasting. Nevertheless serum total protein (TP), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) contents and alkaline phosphatase (ALP) activity keep relatively stable(P>0.05). The content of GLU, protein, lipid and metabolic enzymes activities in serum fluctuated decrease with prolongation of fasting, while Na⁺ and Cl^-content fluctuated increase. The results suggested that large yellow croaker main used body lipid as energy source during fasting period. The nutrient metabolism intensity showed wave-like fluctuated and turn weak as fasting time going by. But the immunity and metabolism function of large yellow croaker were not significantly harmed by long time fasting.