Objective/Background: Improvement is sought for youth with obstructive sleep apnea syndrome (OSAS) who have poor quality of life (QoL), which resolves somewhat following treatment. One mitigating factor in improved QoL following treatment may be adherence to the CPAP protocol, which presents a barrier to most youth. This study explored relations between CPAP adherence and QoL in youth with OSAS. Participants: We recruited 42 youth–caregiver dyads in which youth between the ages of 8 and 16 years were diagnosed with OSAS and required CPAP use as part of their treatment plan. Methods: Following diagnosis of OSAS requiring treatment with CPAP therapy, caregivers completed baseline measures of OSAS-specific QoL. The OSAS-specific QoL domains assessed included sleep disturbance, physical symptoms, emotional distress, daytime function, and caregiver concern. Families received routine CPAP care for three months, after which caregivers again completed measures of OSAS-specific QoL. Adherence data were collected from smartcards within the CPAP machine after three months of treatment. Results: Fifteen youth were adherent to CPAP therapy and 10 were not adherent. CPAP-adherent youth demonstrated significant changes in two domains of OSAS-specific QoL when compared to nonadherent youth: decreased sleep disturbance and decreased caregiver concern. Conclusions: CPAP adherence appears to be associated with positive changes in OSAS-specific QoL domains. It will be important for future research and clinical work to examine strategies for improving CPAP adherence in youth with OSAS.