Immunocompromised persons are at increased risk for severe COVID-19-related outcomes, including intensive care unit (ICU) admission and death (1). Data on adults aged ≥18 years hospitalized with laboratory-confirmed COVID-19 from 10 U.S. states in the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) were analyzed to assess associations between immunocompromise and ICU admission and in-hospital death during March 1, 2020-February 28, 2022. Associations of COVID-19 vaccination status with ICU admission and in-hospital death were also examined during March 1, 2021-February 28, 2022. During March 1, 2020-February 28, 2022, among a sample of 22,345 adults hospitalized for COVID-19, 12.2% were immunocompromised. Among unvaccinated patients, those with immunocompromise had higher odds of ICU admission (adjusted odds ratio [aOR] = 1.26; 95% CI = 1.08-1.49) and in-hospital death (aOR = 1.34; 95% CI = 1.05-1.70) than did nonimmunocompromised patients. Among vaccinated patients,* those with immunocompromise had higher odds of ICU admission (aOR = 1.40; 95% CI = 1.01-1.92) and in-hospital death (aOR = 1.87; 95% CI = 1.28-2.75) than did nonimmunocompromised patients. During March 1, 2021-February 28, 2022, among nonimmunocompromised patients, patients who were vaccinated had lower odds of death (aOR = 0.58; 95% CI = 0.39-0.86) than did unvaccinated patients; among immunocompromised patients, odds of death between vaccinated and unvaccinated patients did not differ. Immunocompromised persons need additional protection from COVID-19 and using multiple known COVID-19 prevention strategies,^† including nonpharmaceutical interventions, up-to-date vaccination of immunocompromised persons and their close contacts,^§ early testing, and COVID-19 prophylactic (Evusheld) and early antiviral treatment,^¶ can help prevent hospitalization and subsequent severe COVID-19 outcomes among immunocompromised persons.