The purpose of this study was to investigate changes in sleep quality, fatigue, mental health, and health-related quality of life (HRQoL) over a two-year period among patients undergoing peritoneal dialysis treatment at home. We further explored the extent to which sleep quality, fatigue, and mental health predicted health-related quality of life outcomes. This prospective study included 55 patients. Sleep parameters changed over two years, independently of treatment. Sleep variables at baseline, to some extent, predicted sleep quality after two years. Daytime sleepiness can be a long-term problem. Findings indicate improvements in nocturnal sleep over a two-year time period, independently of dialysis treatment. In contrast, fatigue remained unchanged over the same time period Dansplantation seems to generally benefit the outcome of HRQoL. Strategies to improve sleep and HRQoL may include systematic risk factor modification and efforts to optimise symptomatic treatment.