Maintenance hemodialysis (MHD) patients often have impaired quality of life (QOL), anxiety, depression, and reduced daily physical activity (DPA) and physical performance. The contributions of these latter factors to reduced QOL in MHD are poorly understood. We examined the association of QOL with anxiety, depression, DPA, and physical performance.Seventy-two relatively healthy adult MHD patients, vintage ≥6 months, and 39 normals of similar age range and gender distribution were studied. QOL was assessed using the Kidney Disease Quality of Life-Short Form (KDQOL-SF). Anxiety and depression were each evaluated with two questionnaires. DPA and physical performance were assessed with a physical activity monitor, Human Activity Profile, and 6-minute walk, sit-to-stand, and stair-climbing tests.Most KDQOL components were reduced in MHD patients versus normals. KDQOL components in patients were commonly inversely correlated with measures of anxiety and depression (P < 0.05) and were more reduced in patients with both anxiety and depression. KDQOL was often impaired in patients with either anxiety or depression. However, most KDQOL scores did not differ between patients and normals without anxiety or depression. DPA, Human Activity Profile, and physical performance often correlated with KDQOL scores in adjusted models, but after further adjustment for anxiety and depression, DPA, Human Activity Profile, and physical performance correlated less frequently with KDQOL scores. This reduction in significant correlations after adjustment for anxiety and depression was particularly pronounced for the association between KDQOL and DPA.In relatively healthy MHD patients, KDQOL scores are usually decreased in those with anxiety and/or depression but are usually normal in those without anxiety or depression. Lower DPA in MHD patients with reduced KDQOL scores often appears to be associated with anxiety and depression. The relationship between QOL and physical performance appears to be less influenced by anxiety and/or depression. These data suggest that treatment of anxiety and depression in MHD patients may improve their QOL, DPA, and possibly physical performance.