Fine control of the number and function of immunosuppressive FOXP3⁺ regulatory T (Treg) cells is critical for the prevention of immune-mediated damage. In this study, we sought to define the molecular control of Treg cell survival and death under inflammatory conditions. We tested the importance of Caspase-8, an essential protease involved in the signal transduction of multiple cell death pathways, specifically in Treg cells by generating Casp8^ΔFoxP3 mice. Under steady-state conditions these mice exhibited marked expansion of Treg cells with an effector phenotype (CD62L^lowPD1^hiICOS^hi), suggesting a pro-apoptotic role for Caspase-8 downstream of death receptors. However, a very different picture emerged under inflammatory conditions. The lymphocytic choriomeningitis virus (LCMV) Docile strain establishes a chronic infection that is controlled, but not cleared, in wild-type mice. By contrast, LCMV infection was fatal in the majority of Casp8^ΔFoxP3 mice, caused by the swift loss of Treg cells, massive activation of virus-specific and non-specific CD8⁺ and CD4⁺ cells and a lethal inflammatory phenotype. Interestingly, those Casp8^ΔFoxP3 mice surviving the inflammatory disease managed to clear the virus. This pro-survival role for Caspase-8 in Treg cells appeared to involve antagonism of necroptosis. The pseudokinase MLKL is a critical effector protein of necroptotic cell death and was induced in Treg cells only upon infection. Compound deletion of Caspase-8 and MLKL rescued the loss of Treg cells and immune defects in LCMV-infected mice. This role for Caspase-8 in protecting Treg cells from necroptosis during inflammation extended to other infection and autoimmune settings. These findings reveal an essential, pro-survival role for Caspase-8 in Treg cells under inflammatory conditions that governs the balance between protective immunity and collateral tissue damage. They also highlight that distinct cell death mechanisms control the homeostasis of Treg cells under steady-state and inflammatory conditions.