To explore an association between sleep quality in children and adolescents undergoing therapy for acute lymphoblastic leukemia (ALL) and polymorphisms in two proinflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor (TNF).Retrospective exploratory analysis using data from a multi-institutional prospective study comparing objective sleep measures by actigraphy over 10 days with retrospective genotyping of IL-6 (-174GC) and TNF (-308GA).Pediatric oncology centers in the southeastern and southwestern United States and in Canada.88 children or adolescents with ALL.Secondary analysis of 88 patients (ages 5-18) with sleep quality measured by actigraphy over 10 days in their home environment and retrospective DNA genotyping.Sleep variables and genotype.IL-6 promoter (-174G>C) C allele was associated with fewer total daily sleep minutes (p = 0.028) and fewer daily nap minutes (p A) or IL-6 (-174G>C) polymorphisms demonstrated disturbed sleep. This study is the first to find a relationship between these two cytokines and disturbed sleep in children and adolescents with cancer.Disturbed sleep among pediatric patients with cancer is multifactoral and includes interactions among environment, medications, and genotype. Additional research should explore serum proinflammatory cytokine levels and the influence of mood and worry on sleep.