Background: Managing the burden of care for patients with chronic debilitating diseases is an important issue. Herein, we assessed the burden in primary family members caring for uremic patients on maintenance peritoneal dialysis. Methods: One hundred seventy caregivers and 170 patients were recruited. Self-perceived scoring along the Zarit Caregiver Burden Scale (ZCBS), World Health Organization Five-item Well-Being Index (WHO-5), and Warwick-Edinburgh Mental Well-being Scale (WEMWBS) were determined for caregivers. Results: There was an inverse relationship between ZCBS and WHO-5 or WEMWBS scores in caregivers, suggesting that the higher the burden, the lesser the self-perceived well-being. One hundred two of 170 caregivers (60%) reported mild to moderate burden, indicating a common presence of mild to moderate caring-related mental and physical stress. Moreover, 31 caregivers (18.2%) reported moderate to severe burden. Several patient disease factors, including diabetes and frailty, increased caregiver burden, while insurance coverage and out-of-pocket medical costs were also positively correlated. Caregivers who lived with patients and spent longer hours in caring-related activities had higher burden scores, while regular exercise seemed to partially alleviate the burden. Conclusion: Our study clearly showed that caring for patients with maintenance peritoneal dialysis caused physical, mental, and social burden in family caregivers, with the extent of the stress being influenced by patients' disease severity and other demographic factors in both patients and caregivers.