Three apparently unrelated cases of Clade I mpox (also known as monkeypox) have been identified in Southern California, state health officials announced in October. All were hospitalized and recovered at home. Several outbreaks of Clade I mpox are ongoing in Central and East Africa. The first case of Clade I mpox in the United States was reported in November 2024, but that individual had recently traveled from East Africa. None of the three new cases in California had recently traveled outside the U.S., suggesting local person-to-person spread. The European Centre for Disease Prevention and Control recently reported the first cases of locally acquired Clade I mpox in Spain, the Netherlands, Italy and Portugal. Clade I mpox has historically had a higher fatality rate than the Clade II type responsible for the large U.S. outbreak in 2022. Health officials say the risk of Clade I mpox remains low for the general U.S. population, but they are urging people at higher risk—including gay men and gender-diverse people—to get two doses of the Jynneos mpox vaccine if they are not already immune.