BACKGROUND This study aimed to investigate the serum levels of inflammatory cytokines in patients with herpes zoster (HZ) and to assess their correlation with the development of postherpetic neuralgia (PHN). Understanding this relationship may offer insight into the mechanisms of PHN and provide avenues for targeted treatment. MATERIAL AND METHODS We selected 169 patients diagnosed with HZ and 43 healthy controls (HCs) for the study. Serum levels of inflammatory cytokines were measured in all participants. Pain severity was evaluated using the visual analog scale (VAS). Based on follow-up data, the 169 HZ patients were categorized into 2 groups: those who developed PHN (HZ-PHN) and those who did not (HZ-Con). We then analyzed the differences in cytokine levels and their correlation with PHN development. RESULTS Compared to the HCs group, HZ patients exhibited a significant decrease in TNF-a levels and an increase in IL-10 levels (P<0.05, P<0.01). The VAS score was negatively correlated with TNF-alpha levels and positively correlated with IL-10 levels in HZ patients (r=-0.3081, P<0.01; r=0.5619, P<0.01). Distinctive levels of TNF-alpha, IL-6, IL-8, and IL-10 were observed among different pain groups (P<0.05, P<0.01). The HZ-PHN group showed lower TNF-alpha and higher IL-10 levels compared to the HZ-Con group (P<0.05, P<0.01). IL-10 level was identified as an independent risk factor for PHN, with a sensitivity and specificity of 76.4% and 54.3%, respectively. CONCLUSIONS Abnormal levels of inflammatory cytokines are present in HZ patients, and the IL-10 level may serve as a valuable indicator for predicting the risk of developing PHN.