Background: Neutropenic fever (FN) is an oncologic emergency associated with significant morbidity and mortality. Patients on chemotherapy are at a higher risk of COVID-19-related complications. During the initial phase of the pandemic, healthcare systems were overwhelmed, resulting in shortage of resources and rationing of care. We aimed to assess the impact of the COVID-19 on trends of hospitalization and outcomes in adult emergency department (ED) visits for cancer-related FN in the US between 2019 and 2020. Methods: In this retrospective observational study using the National Emergency Department Sample of adults presenting to ED for cancer-related FN as primary diagnosis (using ICD-10-CM codes), we compared the outcomes between patients presenting in 2019 (pre-pandemic) and 2020. The primary outcome was mortality. Secondary outcomes were incidence of shock, discharge disposition, and length of stay (LOS). A propensity score matching was performed to estimate the effect of COVID-19 on outcomes. Results: There were a total of 95,163 visits to the ED for FN in 2019 and 2020. Both groups had similar demographics, with mainly White (68.1% vs 69.3%) patients presenting to large metropolitan areas (57.6% vs 58.6%) and mostly metropolitan teaching hospitals (74.5% vs 77.2%). More patients presenting in 2020 had a higher Elixhauser comorbidity index (66.6% vs 70.2% for comorbidity of ≥3; p = 0.0002). Although the number of patients who got admitted or died in the ED was similar in 2019 and 2020 (88.4% vs 87.8% for admission and 0.1% for death, p = 0.83), higher number died during their hospitalization (3.4% vs 4.4%, p = 0.002), and were likely to develop shock (6.0 vs 7.1%, p = 0.005) in 2020. More patients were discharged home with services (21.9% vs 17.1%, p < 0.001), while fewer patients went to nursing homes (7.9% vs 8.5%, p < 0.001) in 2020. There were no significant differences in LOS or cost of hospitalization. A propensity score matching was performed to estimate the effect of COVID-19 on outcomes showing higher mortality during hospitalization (13.7% vs 4.6%, p = 0.006) and increased LOS (6 days vs 5 days, p = 0.02) for patients with concurrent COVID-19. Conclusions: Overall, mortality related to FN was higher during the pandemic and more so among patients with concurrent COVID-19. While patients developing shock was higher in 2020, this was not attributable to COVID. Fewer patients were discharged to nursing homes, and more patients went home with services during the pandemic highlighting the constraints imposed on resources during the pandemic.