Background: HIV, hepatitis B, and hepatitis C are serious infections, but can be treated. The prognosis is much improved by earlier detection and treatment. Prevalence studies have shown that serious mental illness is a risk factor for blood-borne virus infection. Objective: To evaluate the prevalence of blood-borne viral infection in people with psychological disorders attending Aswan Governate. Patients and methods: This across sectional study included 180 patients (150 male, 30 female) with moderate to severe mental illness from the attendants of the Outpatient Clinic of Psychiatric Department, Neuro-Psychiatric Hospital, Aswan Governorate. The study was conducted in the period from May 2019 to November 2019. The etiological diagnosis of the studied group were schizophrenia (males=64, females=9), depression (males=30, females=9) and general anxiety disorder (males=16, females=6). Results: As regard HCV Abs, 157 patients (87.2%) were negative and 23 patients (12.8%) were positive in the studied patients. As regards HBs Ag, there were 162 negative patients (90%) and 18 positive patients (10%) in the studied patients. As regards HIV Abs, there were 170 negative patients (94.4%) and 10 positive patients (5.6%) in the studied patients. There was no statistical significant relation between sex and virology markers in all studied patients (p-value > 0.05). Conclusion: People with serious mental illness are at risk of blood-borne viral infections. Serious mental illness is unlikely to be a sole risk factor and risk of blood-borne viral infection is probably multifactorial and is associated with low socioeconomic status, drug and alcohol misuse, ethnic origin, and sex.