Chronic hepatitis C (CHC) patients treated with peg-interferon alpha and ribavirin (peg-IFN alpha/RBV) complain of irritability, attention and memory disturbances which may indicate cognitive impairment associated with treatment. Aim. Assessment of the probable connection between peg-IFNa/RBV treatment and the development of cognitive disturbances in CHC patients. Method. 47 CHC patients were divided into two groups: experimental (n=26) and control (n=21). The experimental group patients were given peg-IFN alpha 2a (n=18) or peg-IFN alpha 2b (n=8) plus RBV in standard doses as recommended by the manufacturers. Control group patients did not receive the above treatment. Both groups underwent a neuropsychological examination consisting of R. Brickenkamp d2 test, Auditory Verbal Learning Test and Hooper Visual Organization Test at the beginning (t=0) and after 12 weeks of treatment or observation (t=1). Results. The experimental group patients showed significant deterioration in all the measured cognitive functions in t=1 comparing to t=0. Cognitive decline was not seen in the control group. The observed cognitive performance changes could not be correlated sufficiently enough with the presence of organic affective disorders diagnosed according to ICD-10 criteria. Conclusions. The findings suggest that peg-IFN alpha/R-BV therapy of CHC patients is connected with the deterioration in cognitive functioning including attention, auditory verbal memory and visuo-spatial skills. These changes may be the effect of peg-IFN alpha-induced neurotransmission abnormalities in the dorso-lateral prefrontal cortex, anterior cingulate cortex, hippocampus and parieto-orbital cortical regions and can impair patients' ability to drive a motor vehicle, operate machinery, or their engagement in hazardous activities requiring attention and coordination. Medical professionals should thoroughly inform patients about the possibility of cognitive decline associated with peg-IFN alpha/RBV therapy.