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The California Department of Public Health (CDPH) would like to alert healthcare providers, local health jurisdictions and laboratories about three unrelated clade I mpox cases, which have been confirmed in Southern California with no history of recent international travel. Public health investigation indicates that community transmission of clade I mpox is occurring in California. Persons at increased risk of mpox should be encouraged to be vaccinated. Mpox testing should be considered for patients with compatible signs and symptoms (PDF), regardless of vaccination status or previous infection.