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Community-acquired pneumonia is a significant global health concern, responsible for high mortality and morbidity. Recent research has revealed a potential link between disordered microbiome and metabolism in pneumonia, although the precise relationship between these factors and severe community-acquired pneumonia (sCAP) remains unclear. To address this knowledge gap, we conducted a comprehensive analysis using 16S sequencing and liquid chromatography–tandem mass spectrometry metabolomics data to characterize the microbial profile in sputum and the metabolic profile in serum in patients with sCAP. Our analysis identified 13 genera through linear discriminant analysis effect size analysis and 15 metabolites meeting specific criteria (P < 0.05, variable importance projection ≥2, and |Log2 fold change| ≥2). The findings of this study demonstrate the presence of altered coordination between the microbiome of the lower respiratory tract and host metabolism in patients with sCAP. The observed concentration trends of specific metabolites across different disease stages further support the potential involvement of the serum metabolism in the development of sCAP. These correlations between the airway microbiome and host metabolism in patients with sCAP have important implications for optimizing early diagnosis and developing individualized therapeutic strategies. [ABSTRACT FROM AUTHOR]