Early life adversity during infancy influences the development of child and exerts long-lasting effects on physiological functions and vulnerability to psychiatric disorders in particular depression and anxiety. Recent studies also suggest a higher prevalence of metabolic dysfunctions and obesity as well as risks of food addiction in adulthood in subjects exposed to childhood adversity. Maternal separation (MS) in rodents is a well-studied model of early life stress. Several studies demonstrate that chronic MS leads to an exaggerated hypothalamic-pituitary-adrenal axis response to stress and impairs emotional behavior in adult offspring. In contrast, the impact of MS on metabolism and food motivation remain poorly characterized. The aim of the present study was to explore in 2 mouse strains (C57BL/6J and C3H/HeN) differing by their initial maternal behavior, the impact of MS on motivation for palatable food in adult male and female offspring. MS lasted 3 h/day from postnatal day (PND) 2 to PND14 and was combined with a chronic unpredictable stress in dams. We found that MS reduced body weight growth in C3H pups at PDN 15 but had no effect in C57 mice. This effect persisted into adulthood in male C3H but not in females. To investigate MS impact on motivation for palatable food, we used operant conditioning chambers, in which mice, fed ad libitum, must press one (FR1) or several times (Variable Ratio 5, VR10 and VR20) on a lever to obtain a food reward (sweet milk). MS exacerbated the motivation to obtain the palatable reward in male and female C3H mice but not in C57. In conclusion, vulnerability to early stress strongly differs between strain mice. C3H strain seems more susceptible to the long lasting effects of MS on metabolism and on motivation for food reward. Finally, to better understand the brain changes associated with MS in C3H mice, we used microarray to examine gene expression in the hypothalamus, the nucleus accumbens and the medial prefrontal cortex, three regions related to stress and reward functions.