Babesia microti is an obligate intra-erythrocytic parasite transmitted by infected ticks. B. microti is a eukaryote much larger than prokaryotic microbes and more similar to human hosts in their biochemistry and metabolism. Moreover, Babesia spp. possess various immune evasion mechanisms leading to persistent and sometimes life-threatening diseases in immunocompromised hosts. Chronic lymphocytic leukemia (CLL) is the most prevalent adult B-cell malignancy, and a small percentage of CLL transforms into aggressive lymphomas. CLL also causes immune dysfunction due to the over-expansion of immature and ineffective B-cells. When our patient with indolent CLL presented with anemia, pancytopenia, and splenomegaly, all his healthcare providers presumptively assumed a malignant transformation of CLL. However, these are also the signs and symptoms of babesiosis. Herein, we report a case where B. microti infection was presumed as a malignant transformation of CLL and narrowly avoided a devastating outcome. Although the patient developed fulminant sepsis, he finally received the correct diagnosis and treatment. Unfortunately, the disease recrudesced twice. Each time, it became more difficult to control the infection. We describe the clinical course of the case and discuss the case-specific literature review. This report highlights the importance of differential diagnoses ruling out infections which include babesiosis, prior to initiating the treatment of B-cell malignancy.