During November 10–December 3, 2020, five previously healthy children aged 7 months–5 years in Clark County, Nevada, were hospitalized with lethargy and hypoglycemia after vomiting for several days. Clinical findings satisfied criteria for acute liver failure (1), and the children were transferred to a tertiary care children’s hospital for potential liver transplantation. No etiology was identified despite extensive medical evaluations. The Southern Nevada Health District (SNHD) was notified of this unusual cluster, and staff members reviewed medical records and interviewed parents to identify common exposures. Multiple household members from two households reported vomiting within the same time frame as the children, and one adult household member had been hospitalized with unexplained liver abnormalities several months earlier. Further investigation revealed that all patients and symptomatic household members consumed “Re2al Alkalized Water” brand bottled water before illness onset; no other shared exposures were reported.