182 Background: Recent data showed the detrimental effects of COVID-19 infection on various conditions, resulting in a wide range of health disparities and worsening outcomes, as well as an increased burden of cost. However, limited information exists on the impacts of COVID-19 infection on the most commonly admitted with primary cancer, regarding clinical and economic impact. Methods: We analyzed the 2020 U.S. National Inpatient Sample (NIS) to investigate the effects of COVID-19 infection on cases primarily admitted with the most common admitted with primary cancer, using relevant ICD-10 CM codes. Adjusted odds ratios (aORs) for specified outcomes were calculated through multivariable logistic and linear regression analyses. The primary outcome was inpatient mortality, with secondary outcomes including the cost of hospitalization and length of stay. Statistical significance was established at a p-value of 0.05. Results: We estimated 919,104 hospitalizations with a primary discharge diagnosis of cancer conditions. Of these, 0.54% (4,985/919,104) had a concurrent diagnosis of COVID-19 infection and 46.1% were female. The mean age was 63.6 years old and Caucasians dominated the majority of the records (69.7%), followed by Hispanics (13.1%). In a multivariable logistic and linear regression model adjusting for patient and hospital factors, COVID-19 infection was associated with higher in-hospital mortality for all cancer conditions and other outcome. The txable denotes all-type and subpopulation analysis. Conclusions: In conclusion, our study encompasses all most common admitted primary cancer conditions and shed light how COVID-19 infection is associated with higher in-hospital mortality, prolonged hospital stays, and increased economic burden in various condition. Future longitudinal studies are warranted to comprehensively assess the long-term health sequelae in this population. [Table: see text]