This study investigates serum cell-free DNA fluctuations in patients with herpes zoster or post-herpetic neuralgia, offering insight into the tissue damage and inflammatory dynamics associated with these conditions. A single-centre combined cross-sectional and longitudinal study was conducted with 59 patients to assess cell-free DNA levels in herpes zoster and post-herpetic neuralgia. Cell-free DNA was extracted from blood samples of patients with herpes zoster or post-herpetic neuralgia and compared with healthy controls. The findings demonstrated elevated cell-free DNA levels in patients with herpes zoster, which remained elevated for 3 months or longer following treat-ment. These results suggest the presence of a subacute inflammatory state after herpes zoster infection. Furthermore, patients who developed post-herpetic neuralgia did not show elevated cell-free DNA levels, while those who did not develop post-herpetic neuralgia exhibited increased levels. This indicates that post-herpetic neuralgia is likely a localized response to prior nerve damage rather than a systemic inflammatory process with acute tissue damage.