Objectives: To assess the health-related quality of life (HRQOL) and identify the determinants of low HRQOL among Saudi caregivers of children with anxiety disorders. Methods: This study was conducted during October 2019 till January 2020, at four pediatric psychiatry clinics in Aseer Region. It included 220 Saudi caregivers of children with anxiety disorders. A self-administered questionnaire was used for data collection. It comprised the Physical Component Summary (PCS-12) and the Mental Component Summary (MCS-12) scores. Results: There were significantly low PCS-12 and MCS-12 scores among female and illiterate caregivers. PCS-12 and MCS-12 mean scores were significantly lower among caregivers of female children, those with several siblings and those with an illness duration >6 years. Predictors for a low PCS-12 score among caregivers included their educational level and a long duration of the child’s illness, while those for a low MCS-12 score included the child’s gender, their number of siblings, and the duration of their illness. Conclusion: The HRQOL of caregivers of children with anxiety disorders is compromised. Its determinants include mothers, illiterate people, caregivers of female children, caregivers of children with several siblings, and caregivers of children with a long duration of illness. Predictors for low PCS-12 scores among caregivers were their educational level and duration of child’s illness, while predictors for low MCS-12 scores were female gender, large number of siblings, and long duration of anxiety disorders.