The ketogenic diet (KD) is known to reduce ethanol consumption in non-stress conditions (Blanco-Gandía et al. 2021). Therefore, our objective was to assess whether KD modifies stress-induced changes in gene expression and ethanol consumption in female mice. 64 female OF1 mice were categorized into four groups based on the administered diet (KD vs. Standard Diet, STD) and exposure to stress (Vicarious Social Defeat sessions, VSD, vs. Exploration sessions, EXP): STD-EXP (n=16), STD-VSD (n=16), KD-EXP (n=16), and KD-VSD (n=16). The KD-fed mice remained in ketosis from adolescence until the final VSD/EXP session, after which they were switched to a STD. Five weeks after the last VSD episode, mice underwent the oral ethanol self-administration (SA) paradigm and, one day after the completion of SA, striatum and hippocampus tissue samples were collected to determine the expression levels of DRD1, CNR1, CRHR1, OPMR, IL-10, and TLR4 genes. The results revealed that KD diminished the stress-induced increase in ethanol consumption in females. Furthermore, KD prevented the VSD-induced alterations in the expression of DRD1, OPMR, and IL-10 genes in the striatum, as well as TLR4 in the hippocampus. Additionally, KD decreased CRHR1 and increased CNR1 the expression levels of both brain areas. These findings highlight the potential of KD as an effective tool for stress-induced alterations. Further research is needed to fully understand the potential influence of the KD on stress-related responses and susceptibility to addiction, particularly in females.Acknowledgments: PID-2020-112672RB-I00 by MCIN/AEI/ 10.13039/501100011033; Instituto de Salud Carlos III (RIAPAd) RD21/0009/0005; Generalitat Valenciana, PROMETEO (CIPROM/2021/080).