Based on a multidimensional model of the caregiving process, the main goal of this study was to examine the direct and indirect links, via acceptance and denial coping, between the caregiving burden and the quality of life (QoL) in parents of children with asthma. The sample was composed of 182 parents of a child/adolescent between 8 and 18 years of age with a clinical diagnosis of asthma. Data were obtained via self-report questionnaires assessing the caregiving burden, acceptance and denial coping strategies and QoL. Results from structural equation modelling indicated a good fit for the mediation model, which explained 30% of the variability of the parents' QoL. Higher levels of caregiving burden were negatively and indirectly associated with the parents' QoL, via less use of acceptance and greater use of denial coping strategies. Multigroup analyses ascertained the invariance of these links across the children's asthma severity, age and socio-economic groups. These findings emphasise acceptance and denial as important coping mechanisms in the caregiving process. Thus, broad-spectrum family-centred interventions in paediatric asthma settings can target the development of the parents' coping tendencies characterised by greater acceptance and less denial as a way of reappraising caregiving demands as less burdensome and improving their QoL.