question: Background: Malignancy is thought to be an independent risk factor for increased COVID-19 morbidity and mortality. However, neoplastic diseases encompass a heterogenous group of pathologic processes, and further stratification of those patients prone to severe disease is necessary. We sought to identify predictors of poor COVID-19 outcomes among hospitalized patients with malignancy. Methods: We retrospectively reviewed all patients with a diagnosis of hematologic and solid tumor malignancy within the regional Scripps Health hospital system in San Diego County from March 1, 2020 to January 5, 2021 with a PCR confirmed diagnosis of COVID-19. Cancer diagnoses were confirmed via manual chart review;in situ non-melanoma skin cancers were excluded. Only hospitalizations greater than one day were included in the analysis and readmissions were excluded. Outcomes of interest included admission to the ICU, intubation during hospitalization, and death. Associations between outcomes of interest and tumor types, metastatic disease (with or without lung involvement) and those receiving active systemic anticancer therapy (treatment within 3 months of admission) were determined using univariable logistic regression analyses. The study was approved by the Scripps Health Institutional Review Board. Systemic anticancer therapy included cytotoxic chemotherapy, immunomodulators, immune checkpoint inhibitors, and other targeted therapies. Results: Among a total of 2,771 hospitalized patients, 204 (7.36%) met inclusion criteria. The average age was 72.7 years, 48.5% were male, 33.3% were Hispanic and the average BMI was 27.5. The majority of patients (82.8%) had solid tumors, with the most prevalent being breast carcinoma (17.6%) and prostate carcinoma (17.2%). Overall, 21.9% had metastatic disease and 16% had lung involvement. 17.2% had been receiving active cancer systemic treatment. On univariate analysis, patients who were actively receiving treatment had an increased rate of death (37.1% vs 18.9%, OR: 2.5 (1.1-5.5) p= .021). Among patients receiving systemic anticancer therapy, 48.6% received cytotoxic chemotherapy, 5.7% immune checkpoint inhibitors, 22.9% immunomodulators, 17.1% molecularly targeted agents and 2.7% other agents. Moreover, there was a trend towards increased mortality in those with lung involvement (33.3% vs 17.6%, OR: 2.3 (0.9-5.7) p= .067) and those with hematologic malignancy (31.4% vs 20.1%, OR: 0.5 (0.2-1.3) p = 0.146). Conclusions: Among patients hospitalized with a diagnosis of cancer, systemic anticancer therapy was associated with a significantly increased odds of death. Other factors potentially increasing risk of death include hematologic malignancy and solid tumors with lung involvement. Further validation of these findings in a larger sample could impact therapeutic decision making during the COVID-19 pandemic.