Objective: To identify the main determinants of burden and perceived health status in caregivers of Brazilian stroke survivors. Methods: Cross-sectional study. Caregivers answered the Hospital Anxiety and Depression Scale (HADS), Zarit caregiver burden interview (ZCBI) and EuroQol. Patients were assessed with the National Institute of Health Stroke Scale, Barthel index (BI), modified-Rankin scale (m-RS), Mini Mental State Examination and HADS. Results: 200 caregiver-patient dyads were assessed. Caregivers were significantly younger (42 vs. 57.7 years) and had more years of formal education (10 vs. 7.8 years); p < 0.0001. Seventy-seven percent of caregivers were females, and 41% were spouses. The prevalence of anxiety disorders was significantly higher in female caregivers than in males (26.1 vs. 10.9%; p = 0.04). ZCBI mean score was 27.2, and female caregivers had significantly worse scores (28.7 vs. 22.3, p = 0.003). ZCBI mean score significantly increased (worsened) as the severity of the disease, based on m-RS, increased. ZCBI mean scores were significantly higher in wives than in other relatives (31.4 vs. 22.6; ANOVA, p < 0.0001). The EuroQol-5D and EuroQol-Visual Analog Scale mean scores were 0.7 (range: 0.04–0.85) and 75.2 (range: 1–100), respectively. Adequate convergent validity (r = –0.38 to –0.40) between EuroQol and ZBCI mean scores was observed. Patient´s disability (as measured by the BI) and caregiver’s factors (female sex, depression as measured by HADS-depression) were independent predictors of caregiver’s burden (r2 adjusted = 0.48; p < 0.0001) in the multivariate regression analysis. Conclusions: Caregiver’s mood was the most consistent factor influencing caregiver burden and perceived health in stroke caregivers.