Aims and Objectives: This study examined the predictors of caregiver burden based on patient and caregiver characteristics in a sample of Spanish caregivers looking after adult patients with chronic disease. The effect of task type and patient–caregiver interaction is also analysed. Background: Specific predictors of caregiver burden have been widely examined in the literature. Few studies, however, jointly analyse a wide range of factors, including the effect of task type and patient–caregiver interaction. Design: Correlational study.MethodsOne hundred and thirty five informal caregivers for 148 care recipients were recruited from primary health care centres. The caregivers responded to the short version of the Zarit Burden Interview (ZBI), the DEPendency index‐6 Dimensions (DEP‐6D), and reported how long they spent on caregiving on a daily basis. Sociodemographic and health characteristics were also recorded. Linear and logistic regression models were used to evaluate factors associated with ZBI scores and the likelihood of being severely burdened, respectively. This research complies with STROBE guidelines for observational studies. Results: Severe burden was present in 62% of the caregivers. Regression analysis shows that burden severity increases significantly with the level of dependence when the latter is measured either by DEP‐6D or by time spent on basic activities. Care related to incontinence and mobility has the greatest effect on burden, which is aggravated when the patient has behavioural problems. Poor caregiver health or not being retired also contributes to burden levels. Conclusions: These results establish that caregiver burden is related to characteristics of both the caregiver and the care recipient as well as to their interaction.Relevance to clinical practiceThe findings indicate that the socio‐sanitary attention focused on reducing caregiver burden must address the caregiver and patient as a dyad. Identifying the dependence level and the patient's aggressive behaviour can be a good predictor of caregiver burden.