PROJECT SUMMARY/ABSTRACT Amoxicillin is recommended by the World Health Organization (WHO) as adjunctive therapy for the treatment of uncomplicated severe acute malnutrition (SAM). Because children with uncomplicated SAM are more likely to have asymptomatic infection, presumptive treatment with a broad-spectrum antibiotic may be beneficial by clearing any existing infection and improving outcomes. Two randomized placebo-controlled randomized trials have evaluated amoxicillin for uncomplicated SAM and have found conflicting results. These results may indicate either that antibiotics are not helpful for the management of uncomplicated SAM, or that a better antibiotic is needed. Recently, we demonstrated that biannual mass azithromycin distribution as a single oral dose reduces all-cause child mortality in sub-Saharan Africa. Children with uncomplicated SAM, who have an elevated risk of mortality relative to their well-nourished peers, may particularly benefit from presumptive azithromycin treatment. Here, we propose a pilot and feasibility study to evaluate the potential for development of a full-scale randomized controlled trial to test a single dose of azithromycin as compared to amoxicillin and placebo. We anticipate that the results will provide valuable pilot data and allow for refinement of study procedures, allowing for development of a full-scale randomized controlled trial to provide evidence for the role of azithromycin in the management of uncomplicated SAM.