We aimed to determine the relationship between leukocyte counts and the survival of patients with Crimean-Congo hemorrhagic fever (CCHF), a life-threatening illness. This is the first study to do so. A total of 220 patients with CCHF were evaluated retrospectively. The mortality rate was 16.4%. Analysis of the relationship between leukocyte counts and mortality rates provided insight into the pathogenesis of CCHF. Receiving operating curve analysis revealed that leukocyte counts ≥2,950/mm(3) on the day of admission predicted mortality rate with 62.1% sensitivity. The mean hospitalization stay in patients with fatal disease was 4.3 days; therefore, leukocyte counts were compared on the day of admission and day 3 of the hospital stay. Increases in neutrophil levels and decreases in lymphocyte and monocyte levels were identified as significant risk factors for mortality (P = 0.01, 0.037, and 0.001, respectively). The mortality risk was 7-12 fold higher in patients whose levels of leukocytes (2,950 μL), lactate dehydrogenase (967.5 U/L), and alanine aminotransferase (>119.5 U/L) and activated partial thromboplastin time (42.4 s) exceeded the cut-off values; these were identified as independent predictors of mortality. Depletion of monocytes and lymphocytes and accumulation of neutrophils correlated with poor outcome. These results highlight the importance of the mononuclear immune response for the survival of patients with CCHF.