IMPORTANCE The associations between hydration status, intravenous fluid administration, and outcomes of patients infected with Shiga toxin-producing Escherichia coli (STEC) remain unclear. OBJECTIVE To determine the relationship between hydration status, the development and severity of hemolytic uremic syndrome (HUS), and adverse outcomes in STEC-infected individuals. DATA SOURCES MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials via the OvidSP platform, PubMed via the National Library of Medicine, CINAHL Plus with full text, Scopus,Web of Science, ClinicalTrials.gov, reference lists, and gray literature were systematically searched. STUDY SELECTION Two reviewers independently identified studies that included patients with hydration status documentation, proven or presumed STEC infection, and some form of HUS that developed. No language restrictions were applied. DATA EXTRACTION AND SYNTHESIS Two reviewers independently extracted individual study data, including study characteristics, population, and outcomes. Risk of bias was assessed using the Newcastle-Ottawa Scale; strength of evidence was adjudicated using the Grading of Recommendations Assessment, Development, and Evaluation method. Meta-analyses were conducted using random-effects models. MAIN OUTCOMES AND MEASURES Development of HUS, complications (ie, oligoanuric renal failure, involvement of the central nervous system, or death), and interventions (ie, renal replacement therapy). RESULTS Eight studies comprising 1511 patients (all children) met eligibility criteria. Unpublished datawere provided by the authors of 7 published reports. The median risk-of-bias scorewas 7.5 (range, 6-9). No studies evaluated the effect of hydration during STEC infections on the risk for HUS. A hematocrit value greater than 23%as a measure of hydration status at presentation with HUSwas associated with the development of oligoanuric HUS (OR, 2.38 [95%CI, 1.30-4.35]; I2 = 2%), renal replacement therapy (OR, 1.90 [95%CI, 1.25-2.90]; I2 = 17%), and death (OR, 5.13 [95%CI, 1.50-17.57]; I2 = 55%). Compared with putatively hydrated patients, clinically dehydrated patients had an OR of death of 3.71 (95%CI, 1.25-11.03; I2 = 0%). Intravenous fluid administration up to the day of HUS diagnosiswas associated with a decreased risk of renal replacement therapy (OR, 0.26 [95%CI, 0.11-0.60]). CONCLUSIONS AND RELEVANCE Two predictors of poor outcomes for STEC-infected children were identified: (1) the lack of intravenous fluid administration prior to establishment of HUS and (2) a higher hematocrit value at presentation. These findings point to an association between dehydration and adverse outcomes for children with HUS.