During May 17–December 31, 2022, 125 probable or confirmed U.S. monkeypox (mpox)† cases were reported among patients aged <18 years, including 45 (36%) in children aged ≤12 years. Eighty-three cases in persons aged <18 years diagnosed during May 17–September 24, 2022 were previously described (1); 28 (34%) of these were in children aged ≤12 years, 29% of whom did not have reported information on exposure. Among 20 (71%) of 28 patients with documented information on exposure, most were exposed by a household contact. This report updates the previous report using data collected during September 25–December 31, 2022, proposes possible mpox exposure routes in children aged ≤12 years, and describes three U.S. mpox cases in neonates. Household members or caregivers with mpox, including pregnant women and their health care providers, should be informed of the risk of transmission to persons aged <18 years, and strategies to protect persons aged <18 years at risk for exposure, including isolating household contacts with mpox, should be implemented immediately. | | During September 25–December 31, 2022, 17 children aged ≤12 years with probable or confirmed mpox were identified through national surveillance. CDC provided a questionnaire to state and local health departments for collection of the child’s history of exposure to any person with mpox§ during the previous 3 weeks, exposure settings, types of contact (e.g., skin-to-skin, being held or cuddled, diaper change, or toilet use), and precautions taken by the person with mpox (e.g., practiced isolation or covered lesions). This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.¶