This study aimed at evaluating the value of C-reactive protein (CRP) and procalcitonin (PCT) levels in the differential diagnosis of fever in patients with sickle cell disease (SCD). The study included 86 children with SCD (group 1) and 49 controls (group 2). During the study, the patients had 114 acute episodes or routine visits to the units. They were classified as having vasoocclusive crisis with fever (group 1A), vasoocclusive crisis without fever (group 1B), and no crisis or fever (steady state, group 1C). Only patients with crises were admitted to the hospital. Patients admitted to the hospital with various clinical signs and symptoms each and every time were included in groups 1A, 1B, and 1C. Thus, a total of 114 clinical episodes were analyzed. The mean CRP levels in the 3 patient groups were significantly higher than that in the group 2, and among the patient groups, the mean CRP was significantly higher in group 1A than the other groups. The mean CRP level in group 1A and group 1B was significantly higher than that in group 1C. There were no significant differences among the 3 SCD groups in terms of the median serum PCT level; however, the median PCT level in group 1A, group 1B, and group 1C patients was significantly higher than that in group 2 patients. These data indicate that vasoocclusive disease with or without fever apparently does not significantly increase PCT levels in relation to the baseline status of children with SCD, which in turn are clearly more elevated than PCT levels of control children.