Objective: To evaluate the impact of elevated N-terminal pro-brain type natriuretic peptide (NT-proBNP) levels on clinical outcomes in children that met criteria for systemic inflammatory response syndrome (SIRS). Background: NT-proBNP has traditionally been used in adults and children to diagnose and guide the treatment of congestive heart failure. Elevated NT-proBNP levels have been associated with increased morbidity and mortality in adults with septic shock. The association between NT-proBNP levels and morbidity/mortality in children with SIRS has not been studied. Methods: This was a retrospective study. Patient list was generated utilizing ICD-9 and ICD-10 codes of various infectious diagnoses from Jan 2011 to Oct 2017. The inclusion criteria were children (<18 years of age) who presented with suspected infection, met the SIRS criteria and had a NT-proBNP level obtained. Exclusion criteria were final primary diagnoses related to cardiac disease and pre-existing congenital or acquired heart disease. Patients were divided into 2 groups based on elevation of NT-proBNP levels. Variables were compared between 2 groups using Chi-square or non-parametric tests. Results: A total of 4,004 patients were screened and our final cohort consisted of 44 patients. Primary diagnoses were bacterial infection (n=35, 80%), viral infection (n=6, 14%), and Kawasaki disease (n=3, 7%). Between elevated (n=26) and non-elevated (n=18) NT-proBNP groups, there was no difference in age groups, gender, race or final diagnoses. Median NT-proBNP was significantly higher in the elevated group (7,500 vs. 316 pg/mL, p<0.001). Elevated group had higher median C-reactive protein level (208 vs. 70 mg/L, p=0.008) and lower median left ventricular ejection fraction (59% vs. 69%, p=0.002). Children in the elevated group were more likely to require intensive care unit admission (odds ratio 20.0 [95% confidence interval (CI): 2.2 to 181]), mechanical ventilation (OR 5.0 [1.2 to 21.5]), and inotropic support (OR 9.4 [2.2 to 41.5]). One patient died in the non-elevated group and four patients died in the elevated group (p=0.312). Conclusion: Severely elevated NT-proBNP levels were associated with increased morbidity in children with SIRS.