The aim of this study was to investigate the effects of topotecan, a topoisomerase I-inhibiting anticancer agent, on hematologic parameters and serum levels of trace elements. The study was conducted on three groups consisting of 16 and 18 rabbits in the study groups and 15 rabbits in the control group. Rabbits in group I (n = 16) received high-dose topotecan intravenously (i.v.; 0.5 mg/kg once daily), while rabbits in group II (n = 18) received low-dose topotecan i.v. (0.25 mg/kg once daily) for 3 days. The 15 rabbits comprising the control group did not receive topotecan. Serum samples were collected from each rabbit on the first day, before the treatment, and on the 15th day of treatment. Erythrocytes, hemoglobin, white blood cell count, thrombocyte count, and trace elements such as selenium, copper, lead, zinc, and cobalt were analyzed. Hemoglobin levels and erythrocyte counts were lower in both study groups than in the control group. However, thrombocyte and leukocyte counts were similar in all three groups (p > 0.005). Serum trace element levels (copper, lead, zinc, and cobalt) did not differ significantly between groups. However, serum selenium levels were significantly lower in both study groups than the control group (p < 0.001). The results revealed that topotecan treatment causes a decrease in erythrocyte counts and hemoglobin levels due to bone marrow suppression, and these effects must be taken into account during treatment. In addition, selenium supplementation might be helpful in cancer patients receiving topotecan to increase the effect of the chemotherapeutic agent.