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Introduction: Since February 2020, over 104 million people in the United States have been diagnosed with SARS-CoV-2 infection, or COVID-19, with over 8.5 million reported in the state of Texas. This study analyzed social determinants of health as predictors for readmission among COVID-19 patients in Southeast Texas, United States., Methods: A retrospective cohort study was conducted investigating demographic and clinical risk factors for 30, 60, and 90-day readmission outcomes among adult patients with a COVID-19-associated inpatient hospitalization encounter within a regional health information exchange between February 1, 2020, to December 1, 2022., Results and Discussion: In this cohort of 91,007 adult patients with a COVID-19-associated hospitalization, over 21% were readmitted to the hospital within 90  days ( n  = 19,679), and 13% were readmitted within 30  days ( n  = 11,912). In logistic regression analyses, Hispanic and non-Hispanic Asian patients were less likely to be readmitted within 90  days (adjusted odds ratio [aOR]: 0.8, 95% confidence interval [CI]: 0.7-0.9, and aOR: 0.8, 95% CI: 0.8-0.8), while non-Hispanic Black patients were more likely to be readmitted (aOR: 1.1, 95% CI: 1.0-1.1, p  = 0.002), compared to non-Hispanic White patients. Area deprivation index displayed a clear dose-response relationship to readmission: patients living in the most disadvantaged neighborhoods were more likely to be readmitted within 30 (aOR: 1.1, 95% CI: 1.0-1.2), 60 (aOR: 1.1, 95% CI: 1.2-1.2), and 90  days (aOR: 1.2, 95% CI: 1.1-1.2), compared to patients from the least disadvantaged neighborhoods. Our findings demonstrate the lasting impact of COVID-19, especially among members of marginalized communities, and the increasing burden of COVID-19 morbidity on the healthcare system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sandoval, Mikhail, Fink, Tortolero, Cao, Ramphul, Husain and Boerwinkle.)