BACKGROUND: Caregiver stress is harmful to the health of both caregivers and people living with Alzheimer's disease or other dementias. The present study was conducted to assess stress and its predictors of people living with Alzheimer's disease or other dementias' caregivers. METHODS: The present descriptive, analytical, cross-sectional study was conducted in December 2017-June 2018 in Isfahan, Iran. Data were collected by interviewing 99 caregivers had at least 6 months of experience caring for a patient diagnosed with Alzheimer's disease, through questionnaires developed by the researcher. A convenience sample (easy access) of caregivers was recruited from calling the home of formally diagnosed with Alzheimer's patient, that have registered in educational hospitals affiliated to Isfahan University of Medical Sciences and psychiatrists' office both paid caregivers (formal) and unpaid caregivers (family). All caregivers provided informed consent. The type and severity of the relationship between the dependent (stress) and independent variable were assessed using Pearson's and Spearman's correlation coefficients, the independent t-test, and the multivariate regression analysis. RESULTS: The caregivers' mean stress score was 25.4 +/- 10.9 (range: 4-54). About 80% of the caregivers were female. Age and stress score was correlated (P = 0.004), the mean stress score was significantly higher in female caregivers (P = 0.04), informal caregivers (P < 0.001), and significantly lower in the caregivers with previous experience of caring for Alzheimer's patients (P = 0.02) or those introduced by service companies (P = 0.005). Variables including the family relationship with the patient (P = 0.01), kind of caregiving (P = 0.03), and previous experience of caring for Alzheimer's patients (P = 0.04) were stronger predictors of the stress score. CONCLUSION: Stress is a challenge in promoting mental health among dementia caregivers. Providing social support with an emphasis on physical, mental, and social health is mandatory, especially for female and family caregivers, to promote stress management, mental health in this group, and enable optimal and purposeful care.