Fujiogi M, Camargo CA, RaitaY, et al. - Given that in the United States, bronchiolitis is the leading cause of infant hospitalizations, researchers here investigated the interrelationships between major respiratory viruses (and their species), host systemic metabolism, and disease pathobiology. In an ongoing multicenter prospective cohort study, researchers examined 113 infants (63 RSV‐only, 21 RV‐A, and 29 RV‐C) hospitalized with bronchiolitis for their serum metabolome profile. Using sparse partial least squares discriminant analysis, serum metabolites that are most discriminatory in the RSV‐RV‐A and RSV‐RV‐C comparisons were identified. Among 113 infants with bronchiolitis, 639 metabolites were measured. In the RSV‐RV‐A comparison, 30 discriminatory metabolites were identified, predominantly in lipid metabolism pathways (eg, sphingolipids and carnitines). Multivariable models indicated significant correlation of these metabolites with the risk of clinical outcomes (eg, tricosanoyl sphingomyelin, OR for recurrent wheezing at age of 3 years = 1.50). The discriminatory metabolites in the RSV‐RV‐C comparison were also primarily involved in lipid metabolism (eg, glycerophosphocholines [GPCs], 12,13‐diHome). A significant correlation was also observed of these metabolites with the risk of outcomes (eg, 1‐stearoyl‐2‐linoleoyl‐GPC, OR for positive pressure ventilation use during hospitalization = 0.47). Per these findings, the distinct serum metabolomic signatures of respiratory viruses and their species are linked with differential risks of acute and chronic morbidities of bronchiolitis, thereby providing further insight into the complex interrelations between viruses, host systemic response, and bronchiolitis pathobiology.