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Purpose: Chronic cutaneous complications of sulfur mustard (SM) are quite common among intoxicated patients. Among these complications, pruritus represents the most frequent symptom which has significant influence on the quality of life (QoL). The present was undertaken to assess serum levels of substance P in patients who suffer from chronic pruritic lesions due to SM., Methods: For this cross-sectional study, patients suffering from chronic SM-induced pruritic skin lesions (n = 40) and atopic dermatitis (AD)-induced pruritus (n = 20) were recruited. Healthy subjects (n = 10) with no dermatologic disorder were also recruited as control groups. Serum substance P was measured using an enzyme-linked immunosorbent assay. Pruritus severity was assessed using pruritus score and visual analogue scale (VAS). QoL was evaluated using the dermatology life quality index (DLQI)., Results: Significantly elevated serum concentrations of SP were found in the SM compared to the control (p < 0.001) and AD group (p < 0.001). Pruritus score was also higher in the SM compared to both control (p < 0.001) and AD groups (p < 0.001). While there was a higher VAS score in the SM vs. AD group (p = 0.019), no significant difference was observed for DLQI scores (p > 0.05). Significant correlations were found between serum SP and pruritus score in all assessed groups (p < 0.05)., Conclusion: In light of the present findings, elevated SP levels might be regarded as an important contributor of SM-induced chronic pruritus and a potential target for reducing the symptoms.