This study aimed to compare the specificity of the metabolic alterations induced by COVID-19 or Influenza A pneumonia (IAP) in acute respiratory distress syndrome (ARDS).

Our findings support the concept that ARDS is associated with a characteristic metabolomic profile that may discriminate patients with ARDS of different etiologies, being a potential biomarker for the diagnosis, prognosis, and management of this condition.

ARDS due to COVID-19 or to IAP induces a different regulation of amino acids metabolism, lipid metabolism, glycolysis, and anaplerotic metabolism. COVID‐19 causes a significant energy supply deficit that induces supplementary energy-generating pathways.

In contrast, IAP patients suffer more marked inflammatory and oxidative stress responses.

The classificatory model discriminated against the cause of pneumonia with a success rate of 100%.

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