Comorbid depression and anxiety is linked to worse outcomes such as increased impairment, distress, and morbidity, as well as worse treatment outcomes. Transdiagnostic variables such as cognitive fusion are considered potential factors for explaining comorbidity. The aim of this study was to analyze the differences between symptom profiles of caregivers (comorbid, depressive, anxiety, and subclinical) in terms of demographic and contextual factors, stress variables, and cognitive fusion. Individual interviews were conducted with 553 caregivers of a relative with dementia. Sociodemographic variables, stressors, cognitive fusion, and depressive and anxiety symptoms were assessed. Caregivers were grouped into four symptom profiles, comorbid (n = 303), depressed (n = 40) anxiety (n = 86), and subclinical (n = 124), based on their depressive and anxiety symptoms. The likelihood of presenting a comorbid profile relative to the subclinical profile was higher in female caregivers. In addition, higher frequency of disruptive behaviors of the care recipient was a risk factor for presenting a comorbid profile relative to the other three profiles, and higher scores in cognitive fusion were a risk factor of comorbidity relative to the other profiles (anxiety, depressive, and subclinical). The findings suggest that the likelihood of presenting comorbid symptomatology is higher for female caregivers and those reporting higher levels of cognitive fusion and higher frequency of disruptive behaviors. These characteristics may describe a vulnerable profile of dementia family caregivers. (PsycInfo Database Record (c) 2021 APA, all rights reserved).