Abstract Background Severe dehydration due to acute infectious diarrhea remains a leading cause of death among young children worldwide. Diarrhea with severe dehydration is a clinical syndrome with distinct management per the World Health Organization (WHO) Integrated Management of Childhood Illness (IMCI) and the WHO Global Task Force on Cholera Control (GTFCC) guidelines. We sought to characterize the pathogens causing severe dehydration using data from the Global Enteric Multicenter Study. Methods We used the IMCI and GTFCC guidelines to define severe dehydration and quantitative PCR-based (qPCR) attribution models to assign the etiology of diarrhea associated with severe dehydration. Results The IMCI or GTFCC guidelines classified 2,284 (43%) of the 5304 cases with moderate-to-severe diarrhea (MSD) as having severe dehydration. In one third of the cases with severe dehydration no pathogens were attributed. The top pathogens attributed to children with guidelines-classified severe dehydration varied by age and were similar among those requiring IV hydration and hospitalization. Rotavirus (30.9%), Cryptosporidium (12.0%), and ST-ETEC (10.3%) were the most common pathogen for ages 0-11 months, while Shigella/EIEC (25.8%), rotavirus (19.3%), and ST-ETEC (10.9%) were the most common for ages 12-23 months. Shigella/EIEC (25.9%), V. cholerae (10.4%), and rotavirus (9.2%) were the most common among 2–5-year-olds. Conclusions The findings inform prioritization of pathogens, in addition to V. cholerae, that cause severe dehydration for future preventive and treatment efforts. The schema for prioritization is driven primarily by age stratifications.