Varicella-zoster virus (VZV) reactivation or herpes zoster (HZ) results from a decline in cell-mediated immunity. The precise immunological mechanisms driving this reactivation and determining its clinical severity remain unclear. To evaluate the expression of Toll-like receptor 7 (TLR7), serum levels of I interferon response (IFN-a), and the CD4/CD8 T-cell in patients with active HZ and to correlate these immunological markers with disease severity. A case control study was conducted with 50 patients with active HZ and 30 healthy controls. Whole blood and serum samples were collected. TLR7 gene expression was quantified using reverse-transcription quantitative real-time PCR (RT-qPCR), and the serum concentrations of IFN-a, soluble CD4 (sCD4) and soluble CD8 (sCD8) were quantitatively measured by sandwich enzyme-linked immunosorbent assay (ELISA). Patients with HZ exhibited significant upregulation of TLR7 gene expression (p=0.0102) and elevated serum IFN-a levels (p<0.0001) compared with controls. While IFN-a levels did not correlate with clinical severity, both CD4+ (p=0.018) and CD8+ (p=0.016) T cell levels increased significantly with greater disease severity. Sex-specific differences were observed, with males showing higher sCD4 levels and females showing higher sCD8 levels. In conclusion, the adaptive T-cell-derived response, rather than systemic IFN-a levels, is more closely associated with the clinical severity of herpes zoster. The paradoxical upregulation of TLR7 during active disease suggests a complex host–virus interaction involving potential viral evasion mechanisms. These preliminary findings, although limited by sample size, suggest that the sCD4/sCD8 balance and sex-specific immune profiles warrant further investigation as potential prognostic indicators in larger validation cohorts