The use of inflammatory markers (IMs) in the pediatric emergency department (PED) is broad and non-specific. This retrospective, cross-sectional study of children aged 3 months to 18 years evaluated the use of IMs in the PED. The reasons for IM use were provider practice (38%), ruling out a differential diagnosis (36%), and presence of comorbidities (18%). IMs are commonly used for gastroenterology, infectious diseases, and orthopedic diseases. A third had IMs without an indication. Forty-six percent of IM testing was indicated based on medical documentation, of which only 21% had abnormal IMs. Compared to the abnormal IM values by the on-site laboratory, the IM assessment using a receiver operating characteristic (ROC) curve threshold criterion had improved specificity and negative predictive value (NPV) based on the reason for IM use. This study suggests that the rate of abnormal IMs is low and does not affect patient outcomes in the PED.