Abstract Patients with small, non-debilitating strokes often report a reduction in quality of life due to persistent cognitive and emotional alterations. Stroke may directly damage limbic circuitry resulting in an impaired stress response, however the possibility that this may in part explain the prevalence of stroke comorbidity with mood disorders has yet to be determined. Here we systematically examine psychosocial consequences of prefrontal lesions targeting the left anterior cingulate cortex (ACC) using hormone assays and a behavioral test battery in adult rats to probe whether a small stroke could alter stress behavior or response to psychosocial stress (chronic mild stress (CMS) or subordination stress). Minor stroke produced chronic hyperactivity in an open field but did not alter fear-related inhibition in the elevated plus maze. Novelty-induced defecation was increased by the combination of CMS, subordination and stroke. Anterior cingulate lesions alone increased distress vocalizations in the water maze. Interestingly, ACC stroke caused hyper-secretion of porphyrin and long-term hormonal alterations that resulted in adrenal hypertrophy and enhanced dexamethasone suppression of the HPA axis. We propose that this behavioral profile is consistent with an animal model of post-stroke distress-like syndrome which could be useful in understanding how stroke affects the capacity to cope with psychological stress.