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Objectives: disturbances in oxidant and anti-oxidant trace elements is known to cause caricinogenesis and increase tumor invasiveness.This study aimed to assess serum copper (Cu), zinc (Zn) and nitric oxide (NO) level in patients with chronic lymphocytic leukemia (CLL). Methods: Cu and Zn concentrations in the serum of 25 patients CLL and 15 healthy individuals were measured by atomic absorption spectrometry and Serum NO level was assayed by enzymatic one-step method. Results: We found a significant decrease in the mean serum Zn and increase in the mean serum level of Cu and NO. Zn level in CLL patients as compared with the control group (46.4 ±19.8 vs.82.8±9.6 μg/dl) .Cu level was 125.7±36.3 vs 80.4±48.8 .NO level in CLL patients was 161.2±86.8 vs 19.8±16.7 in control subjects. We found significant negative correlation between serum Zn and the disease stage. After chemotherapy serum Zn increased and Cu level decreased significantly while NO level remained elevated. Serum Cu was higher in CLL patients with positive expression of CD38 compared with CLL patients with negative expression of CD38, however, no significant difference was found in serum levels of Zn and NO according to CD38 expression. Serum Zn level correlated negatively with serum NO level. Serum Cu correlated negatively with hemoglobin level and reticulocytic count, and positively with LDH and B2-microglobulin. Non-responsive CLL patients had lower serum Zn and higher serum Cu levels compared to responsive patients; NO level was not statistically different in both groups. Conclusion: Our findings suggest that imbalance in Cu and Zn trace element and NO level is associated with CLL and might play a role in disease pathogenesis and intervention therapeutic trials are needed to investigate their role as an adjuvant therapy in treatment of CLL.