Objective:Fatigue in patients with major depression is understudied, although highly prominent. The objective of this study was to investigate the independent correlation of various depressive symptoms with the severity of fatigue in major depression.Methods:Eighty-one patients (70 female/11 male, 40 inpatients/41 outpatients), aged 23-65 years (mean 48.6±10.6), with a DSM-IV main diagnosis of Major Depressive Disorder (М.Ι.Ν.Ι. 5.0.0.) and currently in a Major Depressive Episode [17-item Hamilton Depression Rating Scale (HDRS) score ≥15], were studied. Patients with physical diseases or other fatigue-related conditions were excluded. The 14-item Fatigue Questionnaire (FQ) was used for the assessment of reported fatigue. Factor analysis of all HDRS items was performed. Pearson's correlations between the derived regression factor scores and the FQ score were calculated. Age, gender, and factor scores that significantly correlated with the FQ score entered a multiple regression analysis, with the FQ score as the dependent variable.Results:Factor analysis of HDRS items indicated a 6-factor structure (F1 ‘depressed mood’, F2 ‘middle/late insomnia and somatic anxiety’, F3 ‘anorexia/ weight loss’, F4 ‘general somatic symptoms’, F5 ‘anxiety/hypochondriasis’, F6 ‘early insomnia’). Only factors F1 (items 1,3,7,8), F2 (items 5,6,11) and F4 (items 13,14,17) were significantly correlated with the FQ score (p< 0.05). F1, F2 and F4 turned out to be significant predictors of FQ in the multiple regression, with standardised beta coefficients of 0.291, 0.290 and 0.278 (p< 0.05), respectively.Conclusions:Depressed mood, somatic anxiety, middle and late insomnia correlate independently with the severity of fatigue reported by patients with major depression.