Background: COVID-19 pandemic has resulted in a global health crisis with widespread mortality and morbidity. Patients with chronic leukemias (CL) are at an increased risk for severe outcomes due to their compromised immune system. Despite the potential impact of COVID-19 on this population, there is a scarcity of information on the outcomes for CL patients. Our study aims to evaluate the mortality and morbidity of COVID-19 in CL patients in the United States. Methods: In this retrospective cohort study, we employed the National Inpatient Sample database of 2020, the largest inpatient database in the United States, to include adult patients (age ≥ 18 years) with chronic leukemias (CL) who were hospitalized for COVID-19, as identified by ICD-10-CM codes. The primary outcome was all-cause in-hospital mortality, while the secondary outcomes were acute respiratory failure (ARF) and the requirement for mechanical ventilation (MV). To identify the predictors of mortality, we conducted multivariable logistic regression analyses, with a p-value of less than 0.05 being considered statistically significant. Additionally, we conducted sensitivity analyses based on the type of CL (chronic lymphocytic leukemia (CLL) or chronic myeloid leukemia (CML)) and the remission status (in remission, not achieved remission, and relapse). The statistical analysis was performed using STATA software. Results: Among 91,375 patients with CL, 5.2% were hospitalized for COVID-19, with 87% of these patients having CLL. The majority of the CL patients (88.6%) had not achieved remission. The mean age of the patients was 72.7 years, with 62.4% being male and 78.9% being white. The mortality rate among CL-COVID-19 patients was 17%, with no significant difference in mortality rates between patients with and without CL (odds ratio [OR] 0.96, 95% confidence interval [CI] 0.81-1.14, p-value 0.65). About 61.5% of CL-COVID-19 patients had ARF and only 10.5% required MV. Patients with CL showed a 16% increase in the odds of ARF (OR 1.16, 95% CI 1.01-1.32, p-value 0.03) while no significant difference was found in the odds of MV. Sensitivity analysis showed no significant differences in mortality, ARF, or MV rates between CLL and CML groups. Another analysis by remission status revealed that patients who had not achieved remission had higher odds of ARF (OR 1.64, 95% CI 1.09-2.46, p-value 0.018) compared to those in remission or relapse. Conversely, patients in remission had a significantly lower likelihood of ARF (OR 0.63, 95% CI 0.41-0.97, p-value 0.036). No significant differences in mortality and MV odds were found according to remission status. Conclusions: Our findings emphasize the importance of vigilant monitoring and management of CL patients during the COVID-19 pandemic, particularly for those who have not achieved remission, to reduce their risk of severe respiratory outcomes.