The first U.S. case of COVID-19 attributed to the Omicron variant of SARS-CoV-2 (the virus that causes COVID-19) was reported on December 1, 2021 (1), and by the week ending December 25, 2021, Omicron was the predominant circulating variant in the United States.* Although COVID-19-associated hospitalizations are more frequent among adults,† COVID-19 can lead to severe outcomes in children and adolescents (2). This report analyzes data from the Coronavirus Disease 19-Associated Hospitalization Surveillance Network (COVID-NET)§ to describe COVID-19-associated hospitalizations among U.S. children (aged 0-11 years) and adolescents (aged 12-17 years) during periods of Delta (July 1-December 18, 2021) and Omicron (December 19, 2021-January 22, 2022) predominance. During the Delta- and Omicron-predominant periods, rates of weekly COVID-19-associated hospitalizations per 100,000 children and adolescents peaked during the weeks ending September 11, 2021, and January 8, 2022, respectively. The Omicron variant peak (7.1 per 100,000) was four times that of the Delta variant peak (1.8), with the largest increase observed among children aged 0-4 years.¶ During December 2021, the monthly hospitalization rate among unvaccinated adolescents aged 12-17 years (23.5) was six times that among fully vaccinated adolescents (3.8). Strategies to prevent COVID-19 among children and adolescents, including vaccination of eligible persons, are critical.*.