Pemphigus vulgaris (PV) is a life-threatening, autoimmune blistering disease affecting the skin and mucous membranes, exerting a detrimental effect on the quality of life (QOL). Our aim was to evaluate the psychological status and QOL of patients with PV and investigate Interleukin-6 (IL-6) as a possible contributor to the pathogenesis of pemphigus and associated depression. The study included 22 patients with PV, 21 patients with depression, and 20 normal controls. All the 63 participants were subjected to assessment of their QOL, psychiatric profile, as well as estimation of serum level of IL-6. All (100%) of the included patients with PV had a negative effect on their QOL, which was significant compared with controls (P<0.001). Among patients with PV, 13 patients (59.1%) had depression. IL-6 was non-significantly elevated in the pemphigus group when compared with the controls (P=0.057). QOL was significantly worse in the depressed pemphigus subgroup compared with the non-depressed pemphigus subgroup (P=0.006 and <0.001) respectively. However, IL-6 was non-significantly elevated in the depressed pemphigus subgroup compared with the non-depressed pemphigus subgroup (P=0.095). A marked deterioration in the QOL was observed in patients with pemphigus. More than 50%, but not all, of patients with pemphigus had depression. IL-6 was non-significantly elevated in patients with pemphigus.