Background Lacking data about tumor necrosis factor receptor (TNFR)-associated factor (TRAF) molecules in human inflammatory reactions with in-vitro studies which demonstrated the involvement of TRAF molecules in the pathogenesis of inflammatory diseases. Aim The authors aimed to perform a study evaluating expression of TRAF-2, TRAF-5, and interleukin-6 receptor (IL-6R) in psoriasis vulgaris and evaluate their role in IL-6 pathway involved in psoriasis pathogenesis. Patients and methods This is a case–control study, where 40 patients with psoriasis vulgaris and 40 healthy controls underwent taking of 4-mm punch skin biopsy. The diagnosis was confirmed with hematoxylin and eosin, and immunohistochemistry examination was done using IL-6R, TRAF-2, and TRAF-5 polyclonal antibodies for all specimens. The immunohistochemistry results were analyzed and scored either no staining (score 0) or positive staining (either +1, +2, or +3). Results Tissue level expression of IL-6R, TRAF-2, and TRAF-5 showed highly statistically significant difference between patients with psoriasis vulgaris and healthy controls, with no relation to clinical data, except for TRAF-2 in inflammatory lymphocytes, which showed a statistically significant relation with duration of the disease. There was a statistically significant relation between inflammatory expression of IL-6R and both TRAF-2 and TRAF-5 and a statistically significant relation between keratinocyte's nuclear expression of IL-6R and TRAF-5 only. Conclusion High expressions of TRAF-2 and TRAF-5 in patients with psoriasis vulgaris with IL-6R illustrate their contribution in psoriasis pathogenesis, with no relation to disease severity.