RIPK1 (receptor-interacting serine/threonine-protein kinase 1) is a master regulator of cellular fate: its activation can define whether cells live or die when exposed to cellular stress. RIPK1-mediated cell death leads to disruption of epithelial barriers and release of damage-associated molecular patterns, cytokines, and chemokines, propagating inflammatory and degenerative diseases, such as Alzheimer’s disease, multiple sclerosis and amyotrophic lateral sclerosis. Thus, RIPK1 has emerged as a compelling drug target for the treatment of human neurodegenerative, autoimmune, and inflammatory diseases. The intriguing converse of RIPK1-driven disease pathogenesis and inhibitory therapeutic development, is the recent discovery of humans with complete RIPK1 deletion. Here, patients suffered severe, recurrent mucosal infections, intestinal inflammation, and a 40% mortality rate. The past two decades of research has shed much light on the mechanistic roles of RIPK1, however its role in vivo in pathogen infection remains largely unresolved. Here we explored the role of RIPK1 in controlling infection by the global human and animal pathogen Salmonella Typhimurium, responsible for ~153 million cases of gastroenteritis and 57,000 deaths annually. There is currently no effective vaccine or therapeutics for S. Typhimurium in humans and antibiotics are only indicated if disease is invasive, as treatment can promote convalescent carriage. We showed that in the absence of RIPK1, infection with S. Typhimurium induces highly dysregulated cytokine responses (IFN gamma, TNF, and IL-6), uncontrolled bacterial burden, and significant mortality in mice. Surprisingly, we found that just one allele of RIPK1 is sufficient to rescue mice from this severe disease phenotype, restoring cytokine homeostasis, controlling bacterial load and enabling 100% survival of animals. Importantly, we have demonstrated for the first time that the kinase activity of RIPK1 is dispensable for controlling S. Typhimurium infection, suggesting that the role of RIPK1 in protecting against infection is unrelated to its role in cell death signaling, but rather highly related to its role in inflammatory signaling. This data, along with the recent characterisation of RIPK1-deficient patients, highlights the critical role of RIPK1 in tissue homeostasis, and raises the important question of how the inevitable introduction of RIPK1 inhibitors as therapeutics may impact host susceptibility to microbial infections.