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This correspondence describes a California-wide collaboration to monitor mpox (formerly monkeypox) outbreaks via wastewater-based surveillance. The authors implemented MPXV-specific PCR assays at nine wastewater plants and correlated genomic DNA concentrations in solids with incidence rates during June, August 2022. In five sewersheds, viral DNA was detected at or before the first reported mpox case, with statistically significant correlations found in sites with 10+ positive detection days. The method enabled near real-time public health response, including alert escalation and resource allocation. The authors emphasize wastewater’s value for tracking zoonotic, nonenteric pathogens without reliance on individual testing, especially amid social stigma or minimal symptoms.