To compare the impact of different post-harvest handling methods on volatile and non-volatile compounds, a total of 54 live large yellow croakers were subjected to commercial slaughter (CS), spinal cord cutting (SCC), or spinal cord cutting and bleeding (SCCB). The fish samples were ice-stored for 72 h, followed by the analysis of volatile compounds using gas chromatography-ion mobility spectrometry and non-volatile compounds using LC-MS-based untargeted metabolomics. The results revealed the detection of a total of 28 volatile organic compounds, with 23 being successfully identified, predominantly including alcohols, aldehydes, esters, ketones, and heterocyclic compounds. Substances such as (E)-2-nonenal and 2-butanone are highly sensitive to post-harvest handling methods during ice storage. Furthermore, 943 non-volatile metabolites were identified, showing significant differences in 180, 100, 117, and 186 metabolites across comparisons of SCC 0 h/CS 0 h, SCCB 0 h/CS 0 h, SCC 72 h/CS 72 h, and SCCB 72 h/CS 72 h, respectively. Notably, the altered metabolic pathways mainly involved fatty acid and amino acid metabolism, including pathways like glycerophospholipid metabolism and arginine biosynthesis. This study revealed the potential mechanisms underlying the enhancement of fish quality through spinal cord cutting and bleeding.