Recent studies have suggested improvements in quality of life (QOL) in patients on quotidian dialysis compared with conventional hemodialysis. Few studies have focused on the burden and QOL in caregivers of patients with end-stage renal disease (ESRD) on nocturnal home hemodialysis (NHD). We aim to assess the caregivers’ burden, QOL, and depressive symptoms and to compare these parameters with their patients’ counterparts. Cross-sectional surveys were sent to 61 prevalent NHD patients and their caregivers. Surveys assessed demographics, general self-perceived health using the 12-Item Short Form Health Survey (SF-12) and the presence of depression using the Beck Depression Inventory. Subjective burden on caregivers was assessed by the Caregiver Burden scale and was compared with perceived burden by the patients. Thirty-six patients and 31 caregivers completed the survey. The majority of caregivers were female (66%), spouse (81%) with no comorbid illness (72%). Their mean age was 51 ± 11 years. Patients were mostly male (64%) with a median ESRD vintage of 60 months (interquartile range [IQR], 18–136 months) and a mean age of 52 ± 10 years. Compared to caregivers, patients had lower perceived physical health score but had similar mental health score. Depression criteria were present in 47% of patients and 25% of caregivers. Total global burden perceived by either caregivers or patients is relatively low. Although there is a relatively low global burden perceived by caregivers and patients undergoing NHD, a significant proportion of both groups fulfilled criteria for depression. Further innovative approaches are needed to support caregivers and patients performing NHD to reduce the intrusion of caring for a chronic illness and the risk of developing depression.