Yu Lee,1 Pao-Yen Lin,1,2 Chih-Yen Chien,3 Fu-Min Fang,4 Liang-Jen Wang5 1Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Institute for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 3Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 4Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 5Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan Objective: The caregivers of patients with head and neck cancer (HNC) may suffer from impaired psychological well-being and a decreased quality of life (QOL) related to the chronic burden of caring for patients’ physical conditions and their mood changes. In this study, we aimed to compare the psychological well-being and QOL between spouse caregivers and non-spouse caregivers of patients with HNC over a 6-month follow-up period.Patients and methods: This study was conducted using a prospective design with consecutive sampling. We recruited study subjects from the outpatient combined treatment clinic of HNC at a medical center in Southern Taiwan. The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, fourth edition was carried out by a trained senior psychiatrist to diagnose caregivers. Furthermore, one research assistant collected the caregivers’ demographic characteristics, clinical data, and clinical rating scales, including the Short Form 36 (SF-36) Health Survey, Hospital Anxiety and Depression Scale (HADS), and Family Appearance, Pulse, Grimace, Activity, and Respiration index at the patients’ pretreatment, as well as their 3- and 6-month follow-up appointments.Results: Of the 143 subjects that successfully completed the study, two-thirds of caregivers were spouses. During the 6-month follow-up period, spouse caregivers demonstrated significantly higher rates of depression diagnosis (p=0.032), higher scores in the depression subscale of HADS (HADS-D) (p=0.010), and lower SF-36 mental component summary (MCS) scores (p=0.007) than non-spouse caregivers. Furthermore, during those 6 months, HADS-D (p=0.007) and the anxiety subscale of HADS scores (p<0.001) significantly decreased, while SF-36 MCS scores significantly increased (p=0.015).Conclusion: The mental health of spouse caregivers of HNC patients was more severely affected than that of non-spouse caregivers during the observed 6-month follow-up period. Therefore, clinicians need to pay more attention to caregivers’ psychological distress during patient care, especially for spouse caregivers. Keywords: spouse caregiver, psychological well-being, quality of life, head and neck cancer, follow-up study