IntroductionDespite the high prevalence of sickle cell disease (SCD) in Brazil, no studies have described the validation of an SCD‐specific health‐related quality‐of‐life (HRQoL) instrument in children. We validated PedsQL 3.0 Sickle Cell Disease Module (PedsQL‐SCD) for Brazilian Portuguese, and cross‐validated it with PedsQL 4.0 Generic Core Scale (PedsQL‐GCS) in children with SCD.MethodsPedsQL‐SCD was translated and culturally adapted using forward and reverse translations. PedsQL‐SCD and PedsQL‐GCS were tested in children and adolescents with SCD aged 2–18 years and their caregivers. Validity was assessed using the Pearson and intraclass correlation coefficients, and reliability measured with Cronbach's alpha.ResultsPedsQL‐SCD was validated in 206 children with SCD (median age 14 years, range: 8–18) and 201 caregivers. Among patients and caregivers, the mean total score for PedsQL‐SCD was 65.7 and 64.1, respectively. The mean total score for PedsQL‐GCS was 73.1 and 68.9 among patients and caregivers, respectively. The internal consistency for PedsQL‐SCD and PedsQL‐GCS was good; Cronbach's alpha coefficients ranged from .59–.93 to .64–.83 among patients and from .60–.95 to .65–.85 among caregivers, respectively. Most intercorrelations between PedsQL‐SCD and PedsQL‐GCS, for patients and caregivers, had medium to large effect sizes (range: .23–.63 and .27–.64, respectively). Pain and pain impact domains of PedsQL‐SCD and physical dimension of PedsQL‐GCS had the highest cross‐correlation (.63 and .6 for patients; .63 and .64 for caregivers, respectively), confirming convergent construct validity.ConclusionPedsQL‐SCD is a valid, culturally appropriate measure to assess HRQoL in children with SCD in Brazil and is well‐correlated PedsQL‐GCS.