Varicella zoster virus (VZV) is the human herpesvirus responsible for varicella and herpes zoster. Herpesviruses encode many inhibitors of cell death pathways, including necroptosis. In cells expressing receptor interacting protein (RIP) 3, necroptosis can occur following death receptor signaling if caspase 8 activity is compromised. The impact of VZV on necroptosis has yet to be investigated. To address this we infected the necroptosis susceptible adenocarcinoma cell line HT-29 with VZV. VZV was able to establish a productive infection in HT-29s, resulting in visible plaques, and the full cascade of viral gene expression was confirmed by immunofluorescence (IFA) staining. Mock and VZV-infected HT-29s were treated with TNF (T), the smac mimetic BV-6 (S) and the pan-caspase inhibitor z-vad-fmk (V) to induce necroptosis and cell death was assessed by measuring ATP levels. Following the induction of necroptosis a significantly higher proportion of VZV-infected cells survived versus mock-infected cells (69% vs. 39%). IFA staining for VZV and phosphorylated mixed linage kinase like protein (p-MLKL), which is induced during necroptosis, was performed following T+S+V treatment of mock and VZV-infected HT-29 cells. Phosphorylated-MLKL was readily observed in mock cells, however within the VZV-infected culture, p-MLKL was predominantly seen in uninfected bystander cells, and only rarely within VZV antigen positive cells. Together these data suggest that VZV can inhibit the necroptosis pathway. The large subunit of the ribonucleotide reductase (R1) encoded by herpes simplex virus (HSV)-1 and 2, encodes a RIP homotypic interaction motif (RHIM), which is essential for blocking necroptosis. The R1 gene in VZV shares a high homology with the C-terminus of HSV R1, however lacks the RHIM domain. We have identified a RHIM-like sequence within a capsid gene of VZV and are currently undertaking studies to determine if this viral gene product is responsible for the observed block in necroptosis mediated by VZV.