Background: Little is known about the course of the symptoms of depression/anxiety and the factors predictive of such courses in hemodialysis (HD) patients. This study aimed at evaluating the possible changes of Beck Depression Inventory (BDI) and Hamilton Anxiety Rating Scale (HARS) over time, and factors associated with such changes in HD patients. Methods: We screened 110 patients for study participation. Of these, 30 were excluded because of dialytic vintage <6 months, alcohol/substance abuse, inability to answer to the questionnaires, diagnosis of psychotic or neurological disorders or recent stressful life events. Eighty patients were included in the study and BDI, HARS, Charlson Comorbidity Index, SF-36 Vitality Subscale, Mini-Mental State Examination (MMSE), routine laboratory parameters, C-reactive protein (CRP) and interleukin-6 were measured at baseline. The 18-month course of BDI and HARS was measured in patients with baseline BDI <=14. Results: At baseline, 42 patients had BDI >14 and 38 patients <=14. In patients with BDI <=14, the BDI decreased/remained stable in 19 and increased in 19. Patients with increased BDI had lower baseline MMSE (22.6 ± 2.6 vs. 25.9 ± 2.7, p=0.004) and higher baseline serum CRP (6.07 ± 4.2 vs. 1.64 ± 1.59, p=0.003). At multivariate analysis the relationship between BDI changes and MMSE and serum CRP was statistically significant. In 25 patients, the HARS decreased/remained stable, while in 13 it increased. Characteristics of the 2 groups of patients did not differ significantly. Conclusions: In a meaningful proportion of HD patients, symptoms of depression worsen over time, and CRP and MMSE are independent predictors of such change.