Background:　Acute　viral　myocarditis　(AVMC)　is　a　common　inflammatory　disease　affecting　the　myocardium　and　is　often　accompanied　by　severe　metabolic　disturbances.　The　molecular　mechanisms　underlying　this　disease　are　complex　and　not　yet　fully　understood.　Methods　and　Results:　Coxsackievirus　B3　(CVB3)-induced　AVMC　mouse　models　were　established.　By　integrating　ultra-high-performance　liquid　chromatography-tandem　mass　spectrometry　(UHPLC-MS/MS)-based　metabolomics　and　data-independent　acquisition　(DIA)-based　proteomics,　we　aimed　to　investigate　the　global　influence　of　CVB3　infection　on　the　myocardial　metabolome　and　proteome　in　mice.　Based　on　the　criterion　of　OPLS-DA　VIP　＞　1.0　and　p　value　＜　0.05,　a　total　of　149　differential　metabolites　(DMs)　were　identified,　including　64　upregulated　and　85　downregulated　metabolites.　Bioinformatics　analysis　revealed　that　these　DMs　were　mostly　enriched　in　Global　and　overview　maps　(Metabolic　pathways),　Energy　metabolism　(Sulfur　metabolism　and　Nitrogen　metabolism),　Amino　acid　metabolism　(Taurine　and　hypotaurine　metabolism,　Lysine　degradation,　and　Arginine　and　proline　metabolism),　and　Carbohydrate　metabolism　(Propanoate　metabolism).　Differential　analysis　also　identified　1385　differential　proteins　(DPs)　between　the　two　groups　(|Fold　Change|　＞1.5　and　p　value　＜　0.05),　including　1092　upregulated　and　293　downregulated　proteins.　Gene　Ontology　(GO)　and　Kyoto　Encyclopedia　of　Genes　and　Genomes　(KEGG)　enrichment　analyses　of　DPs　indicated　that　metabolism-related　pathways　were　significant　components　of　the　AVMC　process.　Next,　we　mined　many　DPs　engaged　in　the　above　metabolic　pathways　through　an　integrated　analysis　of　KEGG　pathway-based　metabolomics　and　proteomics　data.　Conclusions:　Our　integrated　metabolomics　and　proteomics　analysis　revealed　characteristic　alterations　in　metabolites　and　proteins　in　the　myocardium　of　AVMC,　as　well　as　the　associations　between　them.　This　not　only　extends　the　existing　understanding　of　the　molecular　basis　of　the　pathogenesis　and　progression　of　AVMC　but　also　suggests　new　directions　for　its　treatment.