The risk of herpes zoster (HZ) increases with age and declining immune function. Increased oxidative stress and inflammatory conditions may cause negative impact on the immune responses. The present study aimed to assess the levels of oxidative/inflammatory stress biomarkers in HZ patients compared with the controls. This case-control study included 43 HZ patients and 47 age-matched controls. Melatonin (MLT), Indole-dioxygenase (IDO), Interleukin-18 (IL-18), Interleukin-6 (IL-6), ferritin, C-reactive protein (hsCRP), and total homocysteine (tHcy) levels were measured and compared in both groups. The significant high levels of IDO, IL-18, IL-6, ferritin, hsCRP, and tHcy, as well as low levels of MLT were found in HZ patients compared with the controls (p<0.001); these significant differences were also associated with rash and pain severity (p<0.001). The final logistic regression model with the AUC (0.99 [95%CI 0.98-1.00]) showed the association of HZ with decreased level of MLT (OR 0.95; 95%CI 0.92-0.98; p=0.007) and increased levels of tHcy (OR 1.53; 95%CI 1.06-2.19; p=0.02). The findings showed increased inflammation-associated oxidative stress in HZ patients. Elevated tHcy levels and reduced MLT levels may be associated with the manifestation of HZ. More investigations are required to confirm the results. This article is protected by copyright. All rights reserved.