One-quarter of neonatal and infant deaths are due to infection, and the majority of these deaths occur in developing countries. A significant reduction in infant mortality in these countries will not occur without a reduction in deaths due to infection. We participated in a multi-national study that demonstrated the effectiveness of three simplified antibiotic regimens compared to standard treatment. For this report, we examined the site-specific data for the Democratic Republic Congo (DRC), the most impoverished of the countries that participated in the study, to determine if outcomes in the DRC were similar to outcomes across all sites. This randomized controlled trial enrolled 1,842 infants, of whom 1805 met the per-protocol criteria for study analysis. The main outcome was treatment failure within the first week of enrollment. Treatment failure occurred in 123 (6.7%) infants: 30 (6.6%) in Arm A, 36 (8.2%) in Arm B (risk difference 1.6%; 95% CI -1.8% to 5%), 29 (6.3%) in C (-0.3%, -3.4% to 3%), and 28 (6.1%) in C (-0.5%, -3.6% to -2.7%). The risk difference between each of the experimental treatments and the reference treatment suggests equivalence. These findings suggest that a simplified antibiotic regimen can be used for the community-based management of possible severe infection in young infants where referral to a hospital for standard care is often not possible. We speculate that the widespread use of a simplified, community-based treatment could result in increased coverage with treatment and improved survival in poor areas.