It is well-known that early life exposures to biological and/or social stressors may have a long-term impact on adult health. However, the biological mechanisms underlying the developmental origins of health and disease (DOHaD) are not fully understood. Epigenetic mechanisms are good candidates to explain how early events are memorized and induce a phenotype later in life. Various studies have thus shown in mammals that poor nutritional status of parents and low maternal care have an impact on the methylation of genes involved in physiology and in the hypothalamic-pituitary adrenal (HPA) axis in the offspring1,2,3. But the consequences of multiple adversities on epigenetic processes remain to be explored. In this context, our aim was to explore the epigenetic basis (DNA methylation) of maternal obesity combined with maternal separation stress in mice. We study the impact of a combination of maternal obesity and maternal separation on offspring’s physiology, behaviour (emotionality and motivation) and epigenome in C3H mice. Our results indicate that maternal obesity and maternal stress exacerbated anxiety-like behaviour in adult offspring. We hypothesised that epigenetic marks could be one of the molecular bases responsible for the embodiment of early exposure to stress. Currently, we use large-scale transcriptomic (RNA-seq) and DNA methylation (MeDIP-seq) analyses on adult offspring’s liver and nucleus accumbens, which are key organs for energy metabolism and food motivation. Preliminary results show that early life exposure to maternal obesity and stress affect metabolic pathways in liver at transcriptomic and epigenetic levels. Interestingly, we also reported a marked sexual dimorphism in the epigenetic effects of maternal obesity and stress. Our future work will focus on the heritability of these epigenetic marks across generations and their influence on observed phenotype