Objective: The objective of this study was to determine the etiologies and co-morbidities associated with extreme leukocytosis, which is characterized by a white blood cell (WBC) count ≥ 35 × 109leukocytes/L.Method: Retrospective chart review was conducted for all patients, aged 18 years and older, admitted to the internal medicine department between 2015 and 2021 with an elevated WBC count ≥ 35 × 109leukocytes/L within the first 24 hours of admission.Results: Eighty patients were identified to have WBC count ≥ 35 × 109leukocytes/L. The overall mortality was 16% and increased to 30% in those presenting with shock. Mortality increased from 2.8% in patients with WBC count in the range of 35-39.9 × 109leukocytes/L to 33% in those with WBC count in the range of 40-50 × 109leukocytes/L. There was no correlation with underlying co-morbidities or age. Pneumonia was the most common infection (38%), followed by UTI or pyelonephritis (28%) and abscesses (10%). There was no predominant organism responsible for these infections. The most common etiology for WBC count between 35-39.9 × 109leukocytes/L and 40-50 × 109leukocytes/L was infections, while malignancies (especially chronic lymphocytic leukemia) were more common with WBC count > 50 × 109leukocytes/L.Conclusion: For WBC counts in the range of 35-50 × 109leukocytes/L, infections were the main reason for admission to the internal medicine department. Mortality increased from 2.8% to 33% as WBC counts increased from 35-39.9 × 109leukocytes/L to 40-50 × 109leukocytes/L. Overall, mortality for all WBC counts ≥ 35 × 109leukocytes/L was 16%. The most common infections were pneumonia, followed by UTI or pyelonephritis and abscesses. The underlying risk factors did not correlate with WBC counts or mortality.