The hippocampus seems to be affected in MDD, and brain-derived neurotrophic factor (BDNF) has positive effects on neurogenesis within the hippocampus. Although there are inconsistencies among study results, a smaller hippocampal volume in depressed patients is thought to be related to the pathophysiology of the disease. We looked at the correlation between serum BDNF (sBDNF) levels and hippocampal volumes (HCV) of first-episode MDD patients (18 female, 7 male; mean age = 32.1 ± 9.3) and healthy controls (17 female, 5 male; mean age = 29.7 ± 6.4). Region of interest analysis was conducted on the images acquired via MRI. sBDNF levels and HCV correlated only in the MDD group (right: r = 0.46, P = 0.02; left: r = 0.47, P = 0.02); however, HCV did not differ between MDD patients and healthy controls (right: F = 2.45, df = 1.46, P > 0.05; left: F = 0.05, df = 1.46, P > 0.05). BDNF may be a factor underlying HCV differences between MDD and healthy control subjects, which become apparent as severe and multiple episodes are experienced.