AbstractBackground: Equine hepacivirus (EqHV) in equids represents the closest homologue to hepatitis C virus (HCV) infecting humans. A majority ofHCVinfected patients develop a chronic course of infection leading to liver fibrosis, cirrhosis and liver failure. However, in horses mostly transient mild subclinical infections are reported for EqHVto date. Objectives: EqHVcan be involved in chronic liver diseases of horses. Methods: Biochemical parameters in serum samples were measured. Viral load was determined usingqPCR. Next generation sequencing (NGS) of serum was performed. Liver tissue was stained with haematoxylin and eosin and analysed for viralRNAwith fluorescentin situ‐hybridization. Results: The horse showed symptoms of severe hepatopathy and was chronically infected with EqHV. ViralRNAwas detectable in the liver during disease. To rule out other infectious agentsNGSwas performed and showed the highest abundance for EqHV. The identified virus sequence was similar to other circulating equine hepaciviruses. Conclusions: EqHVcan be associated with liver disease in horses. Whether it causes the disease or contributes in a multifactorial manner needs further investigation.