During treatment, children with acute lymphoblastic leukemia (ALL) gain fat mass and lose skeletal muscle mass. The great majority live in low- and middle-income countries with few studies of their body composition and none addressing the hypothesis that the disease itself contributes to nutritional morbidity. At diagnosis, children with ALL were compared to their siblings on socioeconomic status (SES). Nutritional status was assessed by mid-upper arm circumference (MUAC)-for-age Z scores and body composition by dual energy x-ray absorptiometry (DXA). Median SES scores for the patients (47.5) and their siblings (47.0) were very similar (P = 0.5). MUAC Z scores for patients aged >5 years were lower than for siblings (P < 0.001). On DXA siblings had a higher mean appendicular lean mass index Z score, a surrogate of skeletal muscle mass, than patients (P = 0.019). A logistic model to estimate the odds ratio (OR) of being severely/moderately under-nourished (classified by MUAC Z score) by SES revealed that, compared with siblings (n = 49), children with ALL (n = 60) had a higher probability of being under-nourished (OR 5.25, 95% CI 1.44–25.95, P = 0.02). The results support the hypothesis that children at diagnosis of ALL in Guatemala are more nutritionally depleted than their apparently healthy siblings.