Background: Poor physical performance and protein-energy wasting (PEW) are health issues of major concern in haemodialysis patients. The conventional haemodialysis (CHD) regime, three times per week 3-5 h, is subject of discussion because of high morbidity and mortality rates. When patients switch from CHD to longer dialysis sessions, i.e. nocturnal haemodialysis (NHD), improvement in protein intake and increase in body weight is seen. However, it is unclear whether physical performance and more important aspects of PEW, such as body composition, improve as well. Therefore, the aim of this study is to investigate whether physical performance improves and PEW decreases, when patients switch from CHD to NHD. A second aim is to assess the influence of NHD on the biomarkers fibroblast growth factor-23 and sclerostin which are thought to be associated with malnutrition and mortality in patients on haemodialysis. Methods: This study is a prospective multicentre cohort study with an inclusion aim of 50 patients: 25 patients in a control group (three times per week, 3-5 h CHD) and 25 patients in a nocturnal group (three times per week, 7-9 h NHD). Primary outcome is change in physical performance, measured by the Short Physical Performance Battery. Additional measurements are a 6-min walk test, handgrip strength, a physical activity questionnaire and physical activity monitoring. The secondary outcome of the study is PEW, which will be evaluated by body weight, dual-energy X-ray absorptiometry, bio-electrical impedance spectroscopy, mid-upper arm muscle circumference, subjective global assessment, visual analogue scale for appetite and dietary records. Laboratory measurements including fibroblast growth factor-23 and sclerostin, and quality of life assessed with the Kidney Disease Quality of Life-Short Form are also studied. In every patient, four repeated measurements will be performed during one year of follow-up. Discussion: This study will investigate whether physical performance improves and PEW decreases when patients switch from CHD to NHD, compared to a control group who continue treatment with CHD. Strengths of this study are the comparison with a conventional haemodialysis cohort, and the broad variety of objective measurements combined with patient-reported outcomes of physical performance and PEW.