ObjectiveTo evaluate the psychometric properties of the Spanish versions of the child‐ and parent‐report cystic fibrosis questionnaire‐revised (CFQ‐R).MethodsA Spanish adaptation of the CFQ‐R was performed; 68 children with CF (6−13 years) and their parents completed the child‐ and parent‐report CFQ‐R, respectively, and the Revidierter KINDer Lebensqualitätsfragebogen (KINDL) questionnaire. The CFQ‐R was completed twice, 7−10 days apart, and its psychometric properties were analyzed.ResultsThe internal consistency of both CFQ‐R versions was adequate (child‐report version, Cronbach's α >.60 for all domains except “Treatment Burden” [α = .42] and “Social Functioning” [α = .57]; parent‐report version, α > .60 for all domains except “Social Functioning” [α = .58]). For the child‐report version, the lowest measurement error was for “Emotional Functioning” (standard error of measurement [SEM]: 8.3%; minimal detectable change [MDC90]: 19.3%), and the highest was for “Body Image” (SEM: 15%; MDC90: 35%). For the parent‐report version, the lowest measurement error was for “Physical Functioning” (SEM: 7.1%; MDC90: 16.5%), and the highest was for “Weight” (SEM: 17.2%; MDC90; 40.1%). The correlation between the versions showed higher agreement for the domains related to observable signs (“Physical Functioning”) and lower agreement for “Emotional Functioning.” There was a significant correlation between the CFQ‐R and KINDL.ConclusionBoth the child‐ and parent‐report versions of the Spanish CFQ‐R have adequate reliability and validity for clinical and research purposes. These versions can be administered before and after starting modulator therapy to assess its effect on daily functioning. The MDC90 can help identify, with a high probability, whether real changes have occurred in the quality‐of‐life subscales in children with CF.