Background: The importance of biochemical markers such as serum iron and serum albumin in major depressive disorder (MDD) is unclear. We sought to examine the effect of baseline serum iron and serum albumin on depression severity and antidepressant response in MDD. Methods: 308 MDD outpatients (39.5 ± 10.4 years; 168 women) enrolled in an 8-week, 20mg, open trial of fluoxetine had serum iron, serum albumin, height and weight measured at baseline. We assessed the relationship of serum iron and albumin levels at baseline to: 1) depression severity at baseline (as measured by the 17-item Hamilton Depression Rating Scale [HAM-D-17] total score), controlling for age, gender, and BMI, and 2) clinical response, controlling for baseline HAM-D-17. Results: In a multiple regression controlling for age, gender and BMI, lower serum albumin levels predicted greater baseline HAM-D-17 scores (p<0.02); serum iron levels did not predict baseline HAM-D-17 scores (p>0.05). Neither baseline serum iron nor serum albumin levels predicted fluoxetine response (p>0.05). Conclusion: In this open trial of fluoxetine in 308 MDD outpatients, serum albumin predicted greater baseline depression severity, but not clinical response. Serum iron, on the other hand, did not significantly predict either baseline depression severity or clinical response. Future studies on the role of these markers in MDD are warranted. 1. Maes M, Van de Vyvere J, Vandoolaeghe E, Bril T, Demedts P, Wauters A, Neels H. Alterations in iron metabolism and the erythron in major depression: further evidence for a chronic inflammatory process. J Affect Disord. 1996; 40:23-33. 2. Van Hunsel F, Wauters A, Vandoolaeghe E, Neels H, Demedts P, Maes M. Lower total serum protein, albumin, and beta- and gamma-globulin in major and treatment-resistant depression: effects of antidepressant treatments. Psychiatry Res. 1996; 65:159-69.