Background: Erectile dysfunction (ED) is a common disorder leading to serious, negative impact on the quality of the patient's life and self-esteem. Its occurrence rate increases with psoriatic patients, as it is a systemic disease intervenes with endothelial dysfunction. A link is described among systemic inflammation and endothelial dysfunction (Psoriasis), and ED. Objective: Estimate of the serum level of tumor necrosis factor-α (TNF-α) in erectile dysfunction patients with psoriasis and patients with erectile dysfunction without psoriasis. Subjects and Methods: This study was conducted over a period of one year starting from February 2018 until February 2019. The study was consented by the Ethics Committee of Al-Azhar Faculty of Medicine. A sample of 90 men (30 men psoriatic patients with ED and 30 men with ED complaints and 30 healthy men of matched age as controls) were conscripted from the Dermatology and Andrology Outpatient Clinics at Al-Hussien and Bab AlShariah University Hospitals. ED presence and severity were tested by the five-item version of the International Index of Erectile Function questionnaire (IIEF-5). Psoriatic patients were evaluated by PASI score. All subjects had thorough medical history and full physical examination. The serum level of TNF-α was measured for all cases and healthy controls using specific enzyme-linked immunosorbent assay (ELISA) technique. All men volunteered to partake in this study were married and have only one sexual partner. Results: In this study, serum TNF- levels were indicatively elevated in psoriatic patients with ED compared to ED patients only. In addition, the difference reached highly statistical significance between psoriatic patients with ED and healthy controls. The elevation correlates with duration of the disease, and family history. Levels of TNF-α were further increased when ED was associated with psoriasis advocating a more severe course of ED in these patients.