sCD14 is an acute phase reactant; few studies reported its prognostic value in B-CLL patients. This gave us the impetus to conduct this study. This study enrolled 40 newly diagnosed B-CLL Egyptian patients, presented to the Hematology Department of the Medical Research Institute in Alexandria University. The ZAP-70 was determined by flow cytometry whereas serum sCD14 concentration by human sCD14 sandwich ELISA method. The mean serum level of sCD14 was significantly higher among patients with positive ZAP-70, Binet stage C, Rai stage III-IV and high risk CLL prognostic index. It showed a significant positive correlation to the percentage of ZAP-70 expression and significant negative correlation to the hemoglobin concentration. Serum sCD14 concentration could be used to assess B-CLL patients initially as an additional prognostic marker, especially in low resources areas where flow cytometry is not available.