Coxiella burnetii is the causative agent of human Q fever, Australia’s most prevalent zoonotic infection. This intracellular bacterial pathogen establishes a replicative niche by remodelling the host cell lysosome. This is achieved by a large cohort of effector proteins introduced into the host cell via the Dot/Icm Type IV Secretion System. The success of an intracellular bacterial pathogen, particularly slow replicating bacteria such as Coxiella, hinges on their ability to establish and preserve a niche for replication and therefore it is imperative to prevent or delay host cell programmed cell death. Here we established a biological screening platform to identify Coxiella effectors with the capacity to block programmed cell death and promote infection. Multiple effector proteins, with a strong impact on eukaryotic cell survival, have been identified and characterised. This research demonstrates that Coxiella employs novel and distinct strategies to control the human host cell and that we can explore this biological toolbox to develop new knowledge in host-pathogen interactions.