Different types of cell death, including apoptosis, play an important role in the immune defense of arthropods, as infected cells are eliminated, preventing the dissemination of the infectious agent throughout the animal body. The apoptosis can be triggered by two main pathways: the intrinsic or mitochondrial pathway and the extrinsic or death receptor pathway. Both culminate in the activation of the effector caspases, such as caspase-3, resulting, for instance in DNA fragmentation and exposition of markers on the surface of the apoptotic cell, allowing its recognition and elimination by phagocytic cells. To ensure survival and proliferation, microorganisms can inhibit apoptosis of the host cell. The differential proteome of a tick cell line (BME26) in response to an experimental infection with Rickettsia rickettsii, causative agent of the severe Rocky Mountain spotted fever, showed that pro-apoptotic proteins are downregulated in the beginning of infection (6 h) and upregulated in a later time-point (48 h). We therefore evaluated the effects of infection on classic features of apoptotic cells: the spontaneous fragmentation of gDNA and the activity of caspase-3 and the exposition of phosphatidylserine in BME26 cells after induction with staurosporine, a classic activator of apoptosis. The spontaneous fragmentation of DNA was observed exclusively in non-infected cells. In addition, the activity of caspase-3 and the exposition of phosphatidylserine is lower in infected than in non-infected cells. Caspase-3 activity is also lower in infected IBU/ASE-16 cells, an embryonic tick cell line of one primary vector of R. rickettsii in Brazil, Amblyomma sculptum. Importantly, while the activation of caspase-3 exerted a detrimental effect on rickettsial proliferation in BME26 cells, the enzyme inhibition increased bacterial growth. Together, our results suggest that R. rickettsii controls the apoptosis in tick cells, which seems to be important to ensure the colonization of the vector cell. To the best of our knowledge, this is the first report on the modulation of the apoptosis in a tick cell line upon the infection with a species of the genus Rickettsia.