BACKGROUND: Community-acquired pneumonia (CAP) is a major public health threat globally but is understudied in regions with the highest burden. The host immune response during infection may differ based on the site of infection. We hypothesised that analysis of the plasma metabolome in patients hospitalised with suspected infection could identify host response pathways specific to CAP. METHODS: We analysed the plasma metabolomes of adults admitted to a tertiary care hospital in northeastern Thailand with suspected community-acquired infection. Multivariable linear regression was performed for differential metabolite analyses and the global test was used for pathway analysis comparing patients with CAP non-CAP infections and uninfected controls. The least absolute shrinkage and selection operator (LASSO) was used to identify a parsimonious metabolite prognostic signature that was tested on an internal validation set to predict mortality. RESULTS: 841 metabolites from 107 CAP patients and 152 non-CAP infected patients were analysed. 52 metabolites were differentially abundant between the CAP and non-CAP groups. CAP was characterised by increased metabolites involved in polyamine metabolism and decreased metabolites involved in lipid pathways. 13 pathways were differentially enriched between the CAP and non-CAP groups, consistent with individual metabolite analyses. 40 metabolites and four pathways were associated with CAP-specific mortality. A four-metabolite signature predicted 28-day mortality in CAP (area under the curve 0.79, 95% CI 0.62-0.97). CONCLUSION: In a rural tropical setting, CAP induced a distinct metabolomic state compared to non-CAP presentations of infection that may reflect the activation of select host immune responses.