Objectives To analyze the impact of fatigue on individuals’ global, cognitive, physical, and psychosocial functioning in the long term after hepatitis C virus (HCV) treatment and its relationship with HCV clearance among patients coinfected with HIV and HCV exposed to peg-interferon/ribavirin-containing regimens. Patients and methods The study sample included 107 coinfected patients treated for HCV during follow-up in the French ANRS CO13-HEPAVIH cohort. Analyses used scores from the Fatigue Impact Scale (FIS), assessed before treatment initiation and at last available measure after the end of treatment (2 years in median). Patient proportions with a clinically significant improvement in fatigue impact, defined as a decrease higher than 10 points in the 160-point global FIS score, were compared between HCV clearers and chronic HCV patients (Fisher’s exact test). Relationships between HCV clearance and FIS scores were analyzed in linear regression models adjusted for sex, time since end of HCV treatment, and pretreatment scores. Results Twenty-nine percent of patients showed a clinically significant improvement in fatigue (15/57 in HCV clearers vs. 16/50 in chronic HCV patients, P =0.52). HCV clearance was not significantly associated with FIS scores in multivariate models. Conclusion The role of HCV clearance in coinfected patients’ functional recovery in the long term after peg-interferon/ribavirin treatment may be lesser than expected. Additional studies are needed in patients treated with direct-acting antiviral agents. In the meantime, the effectiveness of palliative care and targeted psychological treatments such as cognitive-behavioral therapy in reducing fatigue impact needs to be assessed in the many HCV-cured patients with HIV exposed to suboptimal interferon-based first-generation therapies.