Fatigue is one of the most common patient-reported symptoms and can result in poor quality of life in patients with the hepatitis B virus (HBV). Little is known about the characteristics of fatigue in Korean patients with HBV. This study's purpose was to examine fatigue severity and explore health issues associated with fatigue in Korean patients with HBV. A mixed-methods research design was used. Quantitative data on fatigue severity were measured using the revised Piper Fatigue Scale (PFS) with 147 participants. Qualitative data on health issues induced by fatigue were collected via interviews with11 participants. Content analysis revealed three categories of health issues (physical, psychological, and social) and eight subcategories. Participants' overall fatigue level was moderate. The cognitive/mood dimension on the PFS had a significant negative correlation with age. Emotional and psychosocial issues associated with HBV-related fatigue may be more prevalent than physical issues in Korean patients.