Background: Shortened telomere length has been observed in a variety of diseases. Our objective was to analyze mean telomere length of patients with major depressive disorder. A key question was whether telomere length varies in different groups of depressive patients. Methods: We obtained blood samples from patients with major depressive disorder (n=54) and healthy subjects (n=20). We isolated genomic DNA and measured mean telomere length using telomere restriction fragments and Southern blotting. We grouped patients according to the therapy they received including total antidepressant dose. Results: Mean telomere length of the entire patient group (7.20±0.61 kb) was significantly shorter than in the control group (7.55±0.54 kb). We observed no significant difference in telomere length among the different patient groups, but each of these patient groups had significantly shorter telomeres than the healthy subjects. Further analysis revealed no significant association between telomere length and illness duration and between telomere length and the severity of depression, as determined by the Hamilton score. Conclusion: These results provide further evidence that major depressive disorder is associated with shortened telomeres. However, differences in the applied therapy, the duration of illness, or the severity of depression do not seem to have any influence on telomere length. Depression and Anxiety 0:1–6, 2010. © 2010 Wiley-Liss, Inc.