Background: COVID-19 has led to several waves of outbreaks over the last 2 years. Cancer patients are among the most vulnerable and have high morbidity and mortality rates. We aimed to determine the association between presenting symptoms and symptom burden and COVID hospitalization outcomes among cancer patients. Methods: We conducted a retrospective cohort study on all adult hospitalized cancer patients during their first admission at our cancer center from March 2020 to May 2021. We reviewed medical charts to identify reported symptoms. We used the Foundry data platform to compile and analyze data, including patient and hospitalization characteristics and outcomes. We used the chi-square test to test differences in categorical variables. Results: Our cohort included 595 patients, 272 with hematologic malignancies (45.7%) and 323 with solid tumor malignancies (54.3%). 52.1% were male, with an age range of 18 to 91 years (median age: 62). 64.2% self-identified as Caucasian, 16.1% as other, 14.3% as African American, and 3.5% as Asian. After univariate analysis, we found that female patients had higher rates of abdominal pain (21.4% vs. 14.5%, p=0.03), GI symptoms (36% vs. 27.4%, p=0.03), and sore throat (14.4% vs. 8.4%, p=0.02) than male patients. Smoking status or Charlson comorbidity score were not associated with any presenting symptoms. Solid tumor patients had higher rates of abdominal pain (26.6% vs. 7.4%, p <0.01) than patients with hematologic malignancies. Patients with hematologic malignancies had higher rates of fever (59.2% vs. 42.7%, p<0.01), cough (66.2% vs. 50.8%, p<0.01), and shortness of breath (53% vs. 41.8%, p<0.01) than solid tumor patients. Solid tumor patients more frequently reported more than 3 symptoms (52% vs. 39.2%, p<0.01) than patients with hematologic malignancies. In terms of COVID outcomes, patients with cough (34.4% vs. 12%, p<0.01), shortness of breath (38.5% vs. 12.9%, p <0.01), and fever (29.1% vs. 20.6%, p=0.02) were more likely to have severe COVID-19. Patients with more than 3 symptoms were more likely to have severe COVID-19 (31.7% vs. 21.3% vs. 7.8%, p< 0.01) than those with 1-3 symptoms or no symptoms. Patients with cough (15.1% vs. 6.4%, p<0.01) and shortness of breath (15.5% vs. 7.9%, p< 0.01) had higher inpatient mortality. Patients with chills (5.8% vs. 12.9%, p< value 0.03) and headache (4.4% vs. 12.7%, p=0.02) had lower inpatient mortality. Conclusions: Our study showed that certain presenting COVID-19 symptoms are associated with patient and clinical characteristics, severity of disease, and inpatient mortality among adult hospitalized cancer patients.