The psychological effects of childhood cancer and its treatment extend to all family members, particularly healthy siblings, of the affected child. Previous studies have reported reduced quality of life and self-esteem, as well as increased death anxiety and loneliness, among these children. This study aimed to compare the severity of chronic fatigue in siblings of children with cancer and in children from families without a seriously ill family member, with consideration of the informant: the child’s self-report or the parent’s proxy report. A total of 113 parent–child dyads participated in this controlled cross-sectional study. The sibling group comprised 65 healthy children whose brother or sister had cancer, and the control group comprised 48 children from families without a seriously ill family member. The groups were matched for the children’s sex and age (7–11 years). Chronic fatigue was assessed using the Chronic Fatigue Severity Questionnaire. Linear mixed-effects models revealed a significant group × informant interaction (p < 0.001). In the control group, parents rated fatigue severity lower (Δ = –10 points) than did the children themselves. In the sibling group, parental ratings were comparable to or higher than the children’s self-ratings (Δ = 2 points, p < 0.001). Parent–child agreement was stronger in the sibling group (r = 0.73, p < 0.001) than in the control group (r = 0.34, p = 0.019). No between-group differences were found in the total fatigue scores based on the children’s self-reports. Siblings reported greater physiological discomfort (p = 0.037), but less decline in general well-being, cognitive comfort, and social functioning than controls (all p < 0.001). The results suggest, that in families of children with cancer, parental assessments of a healthy child’s fatigue differ from the child’s own perception of their condition. Parents tend to rate fatigue as more severe than do the children themselves, whereas the opposite pattern is observed in control families. This informant discrepancy should be considered when assessing the well-being of healthy siblings and when providing psychological support to families affected by childhood cancer.