Background: Depression and pain frequently occur together. The objective of this study was to investigate the effects of depression and pain on the impairment of daily functioning and quality of life (QOL) of depressed patients. Methods: We enrolled 131 acutely ill inpatients with major depressive disorder. Depression, pain, and daily functioning were assessed using the 17-item Hamilton Depression Rating Scale, the Short-Form 36 (SF-36) Body Pain Index, and the Work and Social Adjustment Scale. Health-related QOL was assessed using three primary domains of the SF-36: social functioning, vitality, and general health perceptions. Pearson's correlation and structural equation modeling were used to examine relationships among the study variables. Five models were proposed. Results: In all, 129 patients completed all the measures. Model 5, both depression and pain impaired daily functioning and QOL, was the most fitted structural equation model (chi(2)=9.2, df=8, p=0.33, GR=0.98, AGFI=0.94, TLI=0.99, CFI-0,99, RMSEA=0.03). The correlation between pain and depression was weak (r=-0.27, z=-2.95, p=0.003). Limitation: This was a cross-sectional study with a small sample size. Conclusion: Depression and pain exert a direct influence on the impairment of daily functioning and QOL of depressed patients; this impairment could be expected regardless of increased pain, depression, or both pain and depression. Pain had a somewhat separate entity from depression. (C) 2014 Published by Elsevier B.V.