Background: Atopic dermatitis (AD) negatively affects the quality of life (QoL). However, few studies from Saudi Arabia have assessed the effect AD has on the QoL of pediatric patients. Objective: To determine the psychological impact of AD on pediatric Saudi patients using the Children's Dermatology Life Quality Index (CDLQI). Methods: This cross-sectional was conducted across five tertiary hospitals located across five cities of Saudi Arabia from December 2018 to December 2019. The study included all Saudi patients aged 5-16 years who were diagnosed with AD for at least 6 months prior to visiting the dermatology clinic of the included hospitals. The quality of life in children with AD was assessed using the Arabic version of the CDLQI. Results: A total of 476 patients were included, of which 67.4% were boys. AD had a very large and extremely large effect on the QoL in 17.4% and 11.3% of the patients, respectively; the QoL of only 5.7% of the patients was not impacted due to AD. The average CDLQI score was not significantly different between males and females (9.7 vs. 9.1, respectively; P = 0.4255). Domains related to symptoms and emotions were affected to a greater extent compared with the remaining domains, while the school domain was the least affected. The correlation between age and CDLQI (r = 0.04, P = 0.52) and between the duration of the disease and CDLQI (r = 0.062, P = 0.18) was not significant. Conclusions: This study found that AD affects the QoL of a significant proportion of the Saudi pediatric patients, thereby highlighting the need to consider QoL as a measure of treatment success.