Objectives: The aim of this study is to describe quality of life (QoL), identify predictors of worse QoL and examine QoL changes from diagnosis and the end of induction chemotherapy in acute leukemia pediatric patients. Methods: A prospective study was conducted, including 105 newly diagnosed leukemic patients aged from 2 to 17 years at pediatric department, National Cancer Institute, Cairo University. Parents were interviewed to complete QoL assessment questionnaire using the PedsQL 4.0 Acute Cancer Module. Older children (more than 13 years) were interviewed using the same questionnaire version. Results: Patients had an overall score of a median 39 (range 25–64) that changed by the end of induction (median 41.7, range 0–75). Pain and hurt reported a median score of 12 (range 0-100) at diagnosis and by the end of induction, median score was 75 (range 50-100). Both scores were statistically significant being improved by therapy. Both Cognitive Problems and Perceived Physical Appearance worsen by end of induction. Girls and older children had worse QoL. Conclusions: Girls and older children had worse QoL. Cognitive Problems and Perceived Physical Appearance deteriorate by therapy. Chemotherapy regimens for childhood leukemia are lengthy with medications administered over 2.5–3.5 years, and thus future efforts should focus on longitudinal studies that describe QoL over time within individual patients.