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OBJECTIVE The lack of a consensus definition for neonatal sepsis may complicate the accurate calculation of sepsis-related mortality in infants ≤ 32 weeks of gestation. This study evaluates whether concurrent major comorbidities influenced neonatal sepsis-related mortality in this patient population following a diagnosis of bacteremia or blood culture-negative sepsis. STUDY DESIGN This is a retrospective chart review of infants ≤ 32 weeks of gestation, who were admitted to a single academic network of multiple neonatal intensive care units between January 1, 2012 and December 31, 2015, to determine if concurrent co-morbidities contributed to bacteremia or blood culture-negative sepsis- related morality. Direct comparisons between early-onset sepsis (EOS; ≤ 72 hours) and late-onset sepsis (LOS; > 72 hours) were made. RESULTS In our study cohort of 939 total patients ≤ 32 weeks of gestation, 182 infants were diagnosed with 198 episodes of sepsis and 7.7% (14/182) died. Mortality rates did not significantly differ between neonates with bacteremia or blood culture-negative sepsis (7/14 each group), and those diagnosed with EOS compared with LOS (6/14 vs. 8/14). Nearly 80% (11/14) of infants were transitioned to comfort care prior to their death secondary to a coinciding diagnosis of severe grade 3 or 4 intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, and/or intestinal perforation. CONCLUSION Those with sepsis-related mortality had pre-existing comorbidities that are commonly associated with extreme preterm birth. The contribution of comorbidities to sepsis-related mortality should be considered in future investigations designed to evaluate the efficacy of therapeutics and/or technologies that target sepsis-mediated pathways.