Background: Prolactin (PRL) appears to play a role in the pathogenesis of autoimmune diseases. Limited evidence showed an association between serum PRL levels and the activity of pemphigus vulgaris (PV). This study intends to determine PRL level changes in pemphigus patients during therapy and its correlation with disease type and severity. Methods: In this cohort study, we measured serum PRL levels by enzyme-linked immunosorbent assay (ELISA) in newly diagnosed PV patients at three time points: before therapy initiation and after two and four months. Concomitantly, we estimated disease severity by the Pemphigus Disease Area Index (PDAI). Results: We examined 42 new cases of PV. Among 32 cases who completed the study, mean serum PRL levels at the three time points were 15.9±14.1 ng/mL (before treatment), 16.7±9.8 ng/ mL (2 months after initiation of treatment), and 15.2±9.2 ng/mL (4 months after initiation of treatment). Mean PDAI values were 19.3±12.8 (before treatment), 3.7±6.2 (2 months after initiation of treatment), and 0.6±1.5 (4 months after initiation of treatment). Although the disease activity decreased significantly (P