Ketamine, a rapid acting antidepressant ( Zarate et al. 2006), induces acute hippocampal volumetric changes ( Höflich et al. 2021). Considering the observed link between major depressive disorder (MDD) and a lower hippocampal volume (MacQueen et al. 2011), investigating ketamine-induced neuroplastic changes in this region may contribute to understand treatment effects.In a placebo-controlled, single-blind, crossover study 36 healthy subjects (17males, 23.8±3.75 years) received either 0.5mg/kg racemic ketamine or placebo 4 hours before MRI scans. FreeSurfer7.1 was used for the hippocampal subfield segmentation. Hippocampal volume after ketamine administration were compared to placebo. Subsequently, only the volumes of participants receiving ketamine in the first session (n=19) were compared, assessing effects after at least 2 weeks (28.47 days, SD 38.672).While multivariate ANCOVA showed no significant overall hippocampal volumetric changes, subfield analysis revealed a significant (uncorrected for multiple comparison) acute reduction of the left subiculum body volume (F(1,70)= 8.385, p=0.005) and increased volume of the right molecular and granule cell layers of the dentate gryus (GC-ML-DG)-head (F(1,70)=6.293, p=0.015). Subsequent analysis revealed subacute changes of the GC-ML-DG-head only (F(1,6)=4.877, p=0.034).In conclusion, we found no volumetric change in the whole hippocampus. Nevertheless, a sustained reduction of the GC-ML-DG-head was observed, a subfield, which is associated with anhedonia in MDD (Wu et al. 2023). As ketamine alleviates anhedonia (Lally et al. 2015), our results may indicate a link between ketamine-induced neuroplastic GC-ML-DG-head volume modulation and this therapeutic effect. However, further research in depressed patients is required.