Background: Hepatitis C viral (HCV) infection is associated with systemic inflammation and metabolic complications that might predispose patients to cerebrovascular atherosclerosis and may report neurocognitive complaints. Objective: This case-control study aimed to assess cerebrovascular and cognitive changes in patients with chronic hepatitis C (CHC) infection. Patients and methods: Transcranial color Doppler assessment of cerebrovascular reactivity and cognitive abilities screening instruments (CASI) was conducted in 100 CHC patients and 100 healthy controls. All enrolled patients were evaluated by Fibroscan and the current study employed a cut-off of ≤12.5 kPa for excluding cirrhosis. Results: Compared to controls, CHC patients had significantly lower scores on CASI and its components. Patients had significantly lower-middle carotid artery (MCA) intimal media thickening (IMT), peak systolic velocity (PSV), end-diastolic velocity (EDV), and mean flow velocity (MEV) than controls. Additionally, the total CASI score significantly correlated with PSV and EDV of MCA and negatively correlated with IMT, pulsatility index (PI), and resistance index (RI). Conclusion: CHC patients have impaired cognitive function that may be associated with cerebrovascular affection in absence of cirrhosis. Future multi-center studies with the evaluation of the effect of antiviral on cerebrovascular reactivity and cognitive function in such patients are warranted.