Pediatric oncology patients may be at a higher risk of complications and mortality from sepsis compared with their nononcology counterpart. The aim of this study is to compare characteristics, treatment, and sepsis-related mortality between oncology and nononcology patients presenting to the emergency department (ED). This is a retrospective single-center cohort study including patients <18 years old with a diagnosis of sepsis, severe sepsis, septic shock, or bacteremia presenting to an academic ED between January 2009 and January 2015. A total of 158 patients were included with 53.8% having an underlying malignancy. The primary outcome of the study was in-hospital mortality. Secondary outcomes included ED vital signs, resuscitation parameters, laboratory work, infection site, general practitioner unit, intensive care unit length of stay, and hospital length of stay. Oncology patients had a higher in-hospital mortality (5.9% vs. 2.7%), however, it did not meet statistical significance (p = 0.45). On presentation, oncology patients had a lower respiratory rate (24.33 ± 9.48 vs. 27.45 ± 7.88; p = 0.04). There was a significant increase in the white blood count in oncology patients (4.011 ± 4.965 vs. 17.092 ± 12.806; p < 0.001) with this cohort receiving more intravenous fluids. In the first 6 hours (33.0 ± 27.7 mL/kg vs. 24.9 ± 16.1 mL/kg; p = 0.029) as well as having a higher percentage of vasopressor administration (15.3% vs. 1.4%; p = 0.002). Antibiotics were initiated at an earlier stage in the oncology cohort (1.25 ± 1.95 vs. 3.33 ± 1.97 hours; p < 0.0001). Cancer-free patients had a significantly higher rate of lung infections compared with cancer patients (68.5% vs. 32.9%; p < 0.0001). In terms of infection characteristics, cancer patients had a higher percentage of bacteremia (27.1% vs. 4.1%; p < 0.001). There was no statistical significance regarding mortality between the 2 cohorts. Pediatric cancer patients were found to have a higher incidence of bacteremia and received more aggressive treatment. Copyright © 2019 Elsevier Inc. All rights reserved.