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Leukemoid reaction (WBC 30,000/μL) may indicate significant medical conditions, mostly infectious. Prompted by the lack of population-based data on the presentation, characteristics, and necessary workup in children with leukemoid reaction, we searched the database of a tertiary pediatric medical center for all children presented with at least one WBC count of ≥ 30,000/μL in 2009-2014. Demographic, clinical, and laboratory parameters were recorded. Children admitted with WBC 30,000/μL served as controls. Pneumonia was the most common diagnosis in the leukemoid reaction group, with a 5.5-fold higher prevalence of pleuropneumonia than in the control group. The leukemoid group had a longer average hospital stay (7.5 vs. 5.5 days). Patients with WBC ≥ 50,000/μL had a sixfold higher rate of leukemia than patients with a lower count. There was a significant association of leukemia with low platelet count, low levels of C-reactive protein, and high levels of uric acid and lactate dehydrogenase.Children presented with a leukemoid reaction are at high risk of pneumonia, especially pleuropneumonia, and a long hospital stay. Those with WBC ≥ 50,000/μL have a sixfold higher risk of leukemia. For prompt diagnosis, clinicians should be aware of the variables associated with leukemia. What is Known: • Leukemoid reaction has been associated with infectious diseases. • Leukemoid reaction at presentation in adults is correlated with high morbidity and mortality. What is New: • Children with leukemoid reaction are at high risk of pleuropneumonia. • We did not observe increased mortality in children with a leukemoid reaction.