Chronic psychosocial stress is a risk factor for the development of affective as well as somatic disorders. However, vulnerability to adverse stress effects varies between individuals, with previous negative life events along with genetic predisposition playing a major role. In support, we previously showed that the consequences of chronic psychosocial stress induced by chronic subordinate colony housing (CSC, 19 days) can be amplified by pre-exposing mice to repeated maternal separation during early life. To test the significance of the genetic predisposition on the effects of CSC, mice selectively bred for high (mHAB) and low (mLAB) anxiety-related behavior and nonselected CD1 mice (mNAB) were exposed to CSC in the present study. In confirmation of our previous results, CSC mice of both mHAB and mNAB lines displayed chronic stress-related symptoms including increased adrenal weight, decreased adrenal in vitro ACTH sensitivity, lower plasma corticosterone to ACTH ratio, and increased interferon-γ secretion from isolated mesenteric lymph node cells compared with single-housed controls of the respective line. However, the CSC-induced anxiogenic effect found in mNAB was not confirmed in mHAB mice, possibly due to a ceiling effect in these highly anxious mice. Interestingly, mHAB were not more vulnerable to CSC than mNAB mice, whereas mLAB mice were resilient to CSC as indicated by all of the above mentioned parameters assessed. Taken together, our findings indicate that the genetic predisposition, in this case the innate anxiety of an individual, affects vulnerability to chronic psychosocial stress, with a low-anxiety phenotype mediating resilience to both affective and somatic consequences of CSC.