Hypercortisolism has been associated with impairment of cognitive function in humans with Cushing's syndrome (CS), but there are currently no studies looking into this effect in dogs with CS. The present study evaluated the pattern of cognitive deficits and behavioral changes in dogs with naturally-occurring CS (NOCS). A previously published questionnaire (DISHA - disorientation, changes in interactive behavior, sleep-wake cycle disturbances, house-soiling, and changes in activity) was used to assess cognitive dysfunction (CD) in dogs with recently diagnosed CS, and in age-, sex-, and gonadal status-matched dogs (1:2), according to their owners’ perception. The questionnaire consisted of 32 multiple-choice questions, scored 0 to 96. The higher the score, the higher the severity of CD. The questionnaire included eight categories of behavioral signs, namely: disorientation, social interactions, sleep-wake cycles, house-soiling, compulsive behaviors, depressive behaviors, anxiety, and memory and learning. Of the 57 dogs assessed in the study, 19 were included in the CS group and 38 in the control group. Exclusion criteria for the control group were animals suspected of having CS, chronic glucocorticoid therapy, or glucocorticoid exposure in the past month. Dogs with CS exhibited a higher final score (Wilcoxon test) of cognitive dysfunction (W = 149, p = 0.001), especially, higher memory dysfunction (W = 96, p = 0.01), compulsive behaviors (W = 93, p = 0.04), depressive behaviors (W = 86, p = 0.03), and anxiety (W = 117, p=0.001). There was no correlation between age and CD score in dogs with NOCS (r = 0.32, p = 0.465) and neither control dogs (r = 0.18, p = 0.051). Results suggest hypercortisolism may accelerate neurodegenerative process, thus resulting in more intense behavioral and cognitive changes than those observed in age-matched dogs without CS.