BACKGROUND: Children with moderate acute malnutrition (MAM) are treated with lipid-based nutrient supplements (LNSs) or corn-soy blends (CSBs) but little is known about the impact of these supplements on hemoglobin, iron status, and inflammation. OBJECTIVE: The objective of this study was to investigate the impact of supplementary foods for treatment of MAM on hemoglobin, iron status, inflammation, and malaria. DESIGN: A randomized 2 × 2 × 3 factorial trial was conducted in Burkina Faso. Children aged 6-23 mo with MAM received 500 kcal/d as LNS or CSB, containing either dehulled soy (DS) or soy isolate (SI) and different quantities of dry skimmed milk (0%, 20% or 50% of total protein) for 12 wk. The trial was double-blind with regard to quality of soy and quantity of milk, but not matrix (CSB compared to LNS). Hemoglobin, serum ferritin (SF), serum soluble transferrin receptor (sTfR), serum C-reactive protein (CRP), serum α1-acid glycoprotein (AGP), and malaria antigens were measured at inclusion and after supplementation. RESULTS: Between September 2013 and August 2014, 1609 children were enrolled. Among these, 61 (3.8%) were lost to follow-up. During the 12-wk supplementation period, prevalence of anemia, low SF adjusted for inflammation (SFAI), elevated sTfR, and iron-deficiency anemia decreased by 16.9, 8.7, 12.6 and 10.5 percentage points. Children who received LNS compared to CSB had higher hemoglobin (2 g/L; 95% CI: 1, 4 g/L), SFAI (4.2 µg/L; 95% CI: 2.9, 5.5 µg/L), and CRP (0.8 mg/L; 95% CI: 0.4, 1.2 mg/L) and lower sTfR (-0.9 mg/L, 95% CI: -1.3, -0.6 mg/L) after the intervention. Replacing DS with SI or increasing milk content did not affect hemoglobin, SFAI, sTfR, or CRP. CONCLUSION: Supplementation with LNS compared to CSB led to better hemoglobin and iron status, but overall prevalence of anemia remained high. The higher concentrations of acute-phase proteins in children who received LNSs requires further investigation. This trial was registered at www.controlled-trials.com as ISRCTN42569496.