Among diverse profound impacts on patients' quality of life (QoL), end-stage renal disease (ESRD) frequently results in increased levels of depression, anxiety, and stress. Renal replacement therapies such as hemodialysis (HD) and transplantation (TX) are intended to enhance QoL, although their ability to alleviate psychological distress remains uncertain. This research posits the existence of a significant correlation between negative emotional states and QoL among ESRD patients, with varying effects observed in HD and TX patients. To examine the relationship between QoL and negative emotional states (depression, anxiety, and stress) and predicted QoL in various end-stage renal replacement therapy patients with ESRD. This cross-sectional study included HD or TX patients in the Eastern Region of Saudi Arabia. The 36-item Short Form Survey and Depression Anxiety Stress Scale (DASS) was used for data collection, and correlation and regression analyses were performed. The HD and TX transplantation groups showed statistically significant inverse relationships between QoL and DASS scores. HD patients with high anxiety levels and less education scored low on the physical component summary (PCS). In addition, the results of the mental component summary (MCS) were associated with reduced depression. Compared with older transplant patients, TX patients' PCS scores were lower, and depression, stress, and negative working conditions were highly correlated with MCS scores. The findings of this study revealed notable connections between well-being and mental turmoil experienced by individuals undergoing HD and TX. The PCS of HD patients is affected by heightened levels of anxiety and lower educational attainment, while the MCS of transplant patients is influenced by advancing age and elevated stress levels. These insights will contribute to a more comprehensive understanding of patient support.