Background: The provision of care to patients with Chronic Kidney Disease (CKD) is profoundly distressing and can exert adverse effects on the physical and mental integrity of family caregivers. The consequences of ministering to individuals dependent on dialysis on the quality of life, the mental distress thereof, and the ensuing family caregivers' general burden have not been entirely characterized. Few studies have been conducted in the Middle East to address quality of life, psychological distress, and overall burden among family caregivers of patients undergoing haemodialysis (HD). In Oman, up to the researcher knowledge no studies have explored caregivers' burden and related variables among these caregivers. Purpose: This study was conducted to describe caregivers' burden and associated factors among caregivers of patients undergoing HD in Oman. It explored the variables (demographic characteristics, clinical characteristics, overall burden, quality of life, and the psychological distress of depression, anxiety, and stress) associated with caregivers of patients undergoing HD. Methods: A descriptive cross-sectional exploratory design was used to describe caregivers' burden and identify demographic and clinical variables, quality of life, overall burden, and psychological distress among caregivers of patients undergoing HD. A sample of 326 unpaid adult family caregivers was recruited from selected dialysis centers in the North Batinah region and Muscat in Oman, using a convenience sampling technique. Data were collected using the Depression Anxiety Stress Scale to measure psychological distress (depression, anxiety, and stress), WHO-QoL BREF to assess the quality of life, and the Zarit Burden Interview scale to measure caregivers' burden. Multiple linear regression was utilized to recognize the caregivers' burden components. Result: The bivariate analysis evinced a significantly strong negative relationship between caregivers' burden and the variables of physical health of the caregivers, perceived satisfaction with health. The same relationship held for four dimensions of QoL: physical, psychological, social, and environmental QoL. It was found that the burden on caregivers was higher when they tended to patients with more dialysis complications and who were unable to assist themselves. The results also indicated that patient physical health and total number of medications had a significantly strong negative relationship with the overall burden. The regression analysis showed that depression, QoL physical, and duration of patient dialysis significantly and positively predict burden, while the variable of degree of satisfaction with health and environmental QoL significantly and negatively predicted burden and accounted for 31.8% of the variance. Conclusion: To lessen the burden on the caregivers, supportive initiatives should be created taking into account the cultural traits of the community