Abnormalities in the endocrine and immune systems are well documented in patients with Major Depressive Disorder (MDD), however, the mechanisms by which the novel antidepressant treatment, ketamine, influences these physiological systems are unclear. This study examined the effects of repeated ketamine infusions on the endocrine and immune systems using the peripheral biomarkers C-reactive protein (CRP) and cortisol. While both depressive symptoms and suicidal ideation were reduced with repeated ketamine treatment, there was no significant change in plasma CRP levels throughout the clinical trial. Morning salivary cortisol did change throughout the clinical trial in a sex-dependent way. Further sex-specific investigation into ketamine's effect on glucocorticoid expression is needed to advance the knowledge of the underlying mechanisms of ketamine's rapid antidepressant effects to more effectively treat patients with depression.