Background The aims of the study are to evaluate the quality of life of mother and grandmother primary caregivers of children with cerebral palsy (CP) and to compare the difference between these two groups of caregivers. Methods We recruited 125 mother and 52 grandmother primary caregivers of children with CP. All the primary caregivers were interviewed with the short‐form 36 (SF‐36) health survey version 2.0 and with researcher‐designed questionnaires for family background. As for the children, social‐demographic characteristics, medical history and the result of a physical examination performed by a paediatric specialist in neurological rehabilitation were also collected. Results Mother and grandmother caregivers scored lower than their counterparts in the general population in both summary scores. Grandmother caregivers had lower scores than mother caregivers in all eight domains and in the two summary scores, with all differences being statistically significant (P < 0.05), except for the domain of the mental component summary score (P = 0.618). The differences were found particularly remarkable in the domains of physical functioning, role physical, bodily pain and also the physical component summary score (P < 0.001). Conclusions The quality of life is significantly unsatisfactory in both mother and grandmother primary caregivers of children with CP; this research provides evidence for the need of the monitoring of these caregivers.