The aims of this study were (i) to examine whether patients with major depressive disorder (MDD) differ from healthy control subjects with respect to isokinetic muscle performance (IMP) as measured by a dynamometer; (ii) to investigate the effect of subchronic treatment on the IMP in depressed patients. Thirty-eight patients with MDD, and 41 sex- and age-matched healthy controls participated in this study. The severity of depression and anxiety levels were evaluated by the Hamilton Depression and Anxiety Scales. Quadriceps and hamstring IMPs were determined by using an isokinetic dynamometer before and after subchronic antidepressant treatment. The patients had lower IMP levels than healthy controls. After treatment for three months with selective serotonin reuptake inhibitors, the IMP levels increased significantly. These findings suggest that (i) MDD may be characterized by reduced IMP levels; and (ii) treatment with antidepressants may increase the IMP levels, as a state marker for depression. It was concluded that (i) isokinetic muscle performance may be used as a state marker for monitoring antidepressant drug effects on MDD; (ii) isokinetic exercise increasing IMP may be used in the treatment of depression.