SummaryBackground Depression and anxiety have been associated with interferon treatment and low treatment adherence.Aim To study the incidence and associated risk factors of depressive and anxiety disorders during pegylated interferon plus ribavirin and treatment adherence in a prospective cohort of 176 patients with chronic hepatitis C patients.Methods Patients were interviewed at baseline using the Structured Clinical Interview for DSM‐IV Mental Disorders and the Patient Health Questionnaire and the Hospital Anxiety and Depression Scale were completed. Both questionnaires were completed also after 4, 12 and 24 weeks of treatment.Results De novo depressive and/or anxiety disorders were diagnosed in 53 (36%) patients, in whom antidepressants and/or anxiolytics were administered. Higher baseline depression‐subscale score (OR = 27.8, 95% CI = 2.82–333), primary education level (OR = 3.1, 95% CI = 1.40–7.03) and being an immigrant (OR = 3.2, 95% CI = 1.12–9.47) were predictors of psychiatric disorders during anti‐viral therapy. The percentage of patients with good adherence was lower in those with depression and/or anxiety (79% vs. 90%, P < 0.04). Only one patient (1%) discontinued treatment because of a major depressive episode. Depression and/or anxiety disorders had no effect on attainment of sustained virological response.Conclusion Early detection and treatment of depressive and anxiety disorders favours good adherence to anti‐viral treatment in hepatitis C.