Objective: The study aimed to evaluate the quality of life (QoL) of caregivers of children diagnosed with CZS and to assess the association of findings with socioeconomic and CZS-associated variables. Methods: This was a cross-sectional, quantitative study, carried out over three days of multidisciplinary care for patients with CZS. Sixty-four participants underwent a quality of life assessment using the World Health Organization Quality of Life questionnaire (WHOQOL-BREF) in Portuguese. Results: Both groups of caregivers attributed regular scores for Global QoL, and all WHOQOL-BREF domains. Among caregivers of children with CZS, QoL correlated with three of the four WHOQOL-BREF domains (psychological health: rho = 0.49, p < 0.001; social relationships: rho = 0.28, p < 0.023; and environment: rho = 0.11, p < 0.006), while general health perception correlated with three other domains (physical health: rho = 0.49, p < 0.001; psychological health: rho = 0.31, p < 0.012; and social relationships: rho = 0.30, p < 0.016). The environment domain was associated with the level of education in this population (p < 0.001). Macular scarring and focal pigmentary retinal mottling were significantly associated with the physical environment (p = 0.039), negative feelings (p = 0.035), support and social aid (p = 0.020). Conclusion: The present study demonstrates that the WHOQOL-BREF is an effective method to evaluate the general perception of QoL among caregivers of children with CZS. Our results also suggest that caregivers of children with CZS do not experience a reduced quality of life compared to caregivers of typically developing children.