Background: Kaposi’s sarcoma (KS) is the most frequent neoplasm in patients with AIDS, responsible for death in about 20–30% of the affected patients. Objective: To determine the frequency of opportunistic infections (OI) and change of CD4+ cell counts in patients with KS treated with chemotherapy compared to a group of matched-pair patients without chemotherapy. Methods: In a prospective study, the clinical courses of 35 HIV-infected patients with KS treated with chemotherapy were compared with 35 matched-pair patients without chemotherapy. Results: During the observation period of 6 months, 11 OI occurred in 10 patients of the chemotherapy group and 5 OI in 5 patients of the control group. With respect to the changes of CD4+ cell counts, no significant differences could be observed. Conclusion: The risk for OI in HIV-infected patients with KS is increased while receiving chemotherapy. This should be reflected upon when chemotherapy is taken into consideration.