Pemphigus vulgaris is a life-threatening, autoimmune blistering disease of the skin and mucous membranes, characterized by painful oral erosions and flaccid skin blisters, it occurs due to IgG autoantibodies against desmoglein 3 (Dsg3), leading to loss of its function, acantholysis of keratinocytes and eventually formation of blisters. Previous studies have been investigated the role of different inflammatory cytokines such as interleukin IL-1, IL-2, IL-6 and TNF-alpha in pemphigus pathogenesis. Since pemphigus is considered a chronic disabling disorder of the skin and mucous membrane, the disfiguring nature of the disease with its presentation with painful oral and cutaneous erosions as well as the resulting difficulty in eating, avoiding people, all exert a detrimental effect on the quality of life. Besides the need for long-term hospitalization, believing that a total cure is impossible, financial burden, and side effects of treatment, may be a cause of different psychiatric disorders such as profound depression which can lead to suicidal ideations. Aim of work: This work aimed to evaluate psychological status and quality of life of pemphigus vulgaris patients, and assess IL6 as a possible agent in pathogenesis of pemphigus and depression. Patients and methods: Twenty two patients with pemphigus vulgaris aged more than 17 years old were included. Their diagnosis was based on a combination of clinical and histopathological examination. Twenty one patients belonging to the depression group aged more than 23 years were also included as controls. Twenty normal controls aged more than 22 years were also included. All the sixty-three participants included in this study were subjected to assessment of psychiatric profile and quality of life using DLQI in pemphigus vulgaris patients and QOL questionnaire in the three study groups to allow for comparison between them, as well as estimation of serum IL6. Results: All (100%) of the included pemphigus patients had a negative effect on their quality of life, there was significant impairment in Quality of life in pemphigus group compared to normal group (P=0.000). Of all pemphigus vulgaris patients, 13 patients (59.1%) had depression, 5 of whom (22.7%) severe depression, 5 (22.7%) moderate depression, 3 (13.6%) mild depression, and 9 (40.9%) were non depressed. There was significant difference in IL6 between the three study groups (P=0.046). Interleukin 6 was non-significantly elevated in the pemphigus group when compared to normal group (P=0.057). Both DLQI and QOL questionnaire were significantly worse in the depressed pemphigus subgroup compared to the non-depressed pemphigus subgroup (P=0.006 and 0.000) respectively. Interleukin6 was non- significantly elevated in the depressed pemphigus subgroup when compared to the non-depressed pemphigus subgroup (P=0.095). Conclusion: In conclusion, there is marked deterioration in quality of life observed in pemphigus patients, in addition to prevalence of depression between them, non-significant elevation of Interleukin 6 in pemphigus patients.