Abstract Background Several lines of evidence suggest that neuroplasticity is impaired in depression and improves with effective treatment. However until now, this evidence has largely involved measures such as learning and memory which can be influenced by subject effort and motivation. This pilot study aimed to objectively measure neuroplasticity in the motor cortex using paired associative stimulation (PAS), which induces short term neuroplastic changes. It is hypothesized that neuroplasticity would improve after effective treatment for depression. Methods Neuroplasticity was measured in 18 depressed subjects before and after a course of anodal transcranial direct current stimulation (tDCS), given as treatment for depression. The relationships between PAS results, mood state and brain-derived neurotrophic factor (BDNF) serum levels were examined. Results Neuroplasticity (PAS-induced change) was increased after a course of tDCS (t(17)=−2.651, p=0.017). Treatment with tDCS also led to significant mood improvement, but this did not correlate with improved neuroplasticity. Serum BDNF levels did not change after tDCS, or correlate with change in neuroplasticity after tDCS treatment. Limitations While this study showed evidence of improved neuroplasticity in the motor cortex after effective treatment, we are unable to present evidence that this change is generalized in the depressed brain. Also, the presence of antidepressant medications and the small sample of patients (n=18) meant the study could not definitively resolve the relationship between neuroplasticity, mood and BDNF. Conclusion This novel preliminary study provides evidence that a treatment course of tDCS can improve neuroplasticity in depressed patients.