Objective: To increase our knowledge of the patient variables related to the overburden of the caregivers of patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPDs). Methodology: This was a cross-sectional study of patients with severe COPD who have informal caregivers. We performed a multivariate analysis of sociodemographic (economic situation, care, dependence, social risk, and use of social services) and clinical (degree of dyspnea, previous hospitalizations, disease impact, pulmonary function, and comorbidity) factors and related these to the burden of informal caregivers, as evaluated using the Zarit scale. Results: The study included 91 patients, age 72.6±8.7 years and 80 were male (89.7%); the mean modified Medical Research Council dyspnea scale (mMRC) score was 2.5±0.8; mean FEV1 was 39.5 ± 13.2%; and 70 patients (76.9%) were dependent for basic activities. Of the informal caregivers, 90 (90.9%) were women, 49 (49.4%) were partners or spouses, and 29 (29.6%) were daughters. The mean Zarit questionnaire score was 51.4±14.2, with 63 of carers (69.2%) perceiving some overburden, and 34 (37.4%) describing the overburden as mild–moderate. The variables related to informal caregiver overburden in the multivariate study were the previous use of social resources [OR = 8.1 (95% CI = 1.03–69.9); p = 0.04], degree of mMRC dyspnea 3–4 [OR =4.7 (95% CI = 1.7–13.2); p = 0.003], and two or more admissions for AEPOC in the previous year [OR = 4.5 (95% CI = 1.7–13.2); p = 0.003]. Of the informal caregivers of patients who had presented two or more of these variables, 92.3% perceived an overburden. Conclusion: The variables associated with overburden are easily accessible in patient medical records, or can be obtained by interviewing patients or their relatives. This informa-tion would allow to detect and assess the overburden of informal caregivers to provide an early warning of this problem. © 2021 Fernández-García et al.