Background: Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are 2 inflammatory indicators that increase in many pathologic and physiologic conditions. Pemphigus vulgaris (PV) is an autoimmune skin disease in which autoantibodies against desmogleins cause acantholysis. In this study we have measured ESR and CRP levels in patients with PV to evaluate the relationship between an increase in these markers and disease severity.Methods: In this cross-sectional study, we selected patients with proven diagnosis of PV who referred to the Dermatology referral clinic, Faghihi hospital, Shiraz, Iran during a one year period. There were 30 patients enrolled in this study who provided blood samples to measure their ESR and CRP levels. We usedthe Mahajan scoring system to determine the disease severity. Results: In 27 (90%) cases, ESR was normal and 20 (66.7%) cases had negative CRP. There was a significant correlation between CRP and PV severity (P=0.015); however, there was no correlation between ESR and disease severity (P=0.126). Conclusion: A correlation existed between CRP and severity of PV. Further studies must be undertaken to prove the prognostic role of CRP in PV. The discovery of new prognostic factors can change the treatment strategy and protocol for PV.