Pemphigus is a group of immune‐mediated blistering diseases of skin and mucus membrane caused by destruction of the intercellular junction (desmosomes) by autoantibodies. Pemphigus vulgaris (PV) is considered the most common type of all pemphigus family. Various cytokines play a major role in pemphigus pathogenesis. Interleukin‐33 (IL‐33) role has been studied in various autoimmune diseases as; psoriasis and rheumatoid arthritis, yet it has not been studied in Egyptian patients with PV. The study aimed to evaluate the possible role of IL‐33 in PV by assessing its level in the serum using ELISA and to detect its correlation with activity score using Pemphigus Disease Area Index (PDAI). Forty‐four patients with PV and 36 age and sex‐matched healthy controls were enrolled in the study. After full history taking and complete dermatological examination, the severity score was calculated using PDAI, then serum samples were taken from each patient and control subjects and subjected to quantitative measurement of serum IL‐33 using ELISA. Serum level of IL‐33 is significantly raised in PV patients compared to control subjects (P‐value = .007). The level of IL‐33 was found to be strongly correlated with the activity of the disease measured by PDAI. IL‐33 might have a role in PV pathogenesis as shown by its rising level in PV patients. In addition, serum level of IL‐33 is strongly correlated with the activity of PV. Thus, we suspect that IL‐33 can be used as marker for monitoring PV severity and measuring treatment efficacy.