Under-five mortality remains a major concern in the world and in Senegal. It is mainly due to preventable and treatable diseases with priority life-saving medicines for under-five children. This study evaluated the availability, management and use of these drugs in two health districts in Senegal. A descriptive cross-sectional study was conducted in the health districts of Guediawaye and Pete from 01 November 2018 to 31 January 2019. The health district of Guediawaye is in the region hosting the Senegalese capital while that of Pete is located in the region of Saint Louis, northern Senegal. Nine drugs that can prevent and treat malaria, diarrhea, pneumonia and malnutrition were selected. An inventory form and a self-administered questionnaire were used to collect data that was analyzed with SPSS and expressed as a percentage and average. Drug availability was 50.4% and 54.3% in Guediawaye and in Pete, respectively. Average stock-out duration in the past three months was estimated at 22.6 and 26 days, respectively. The drug management was marked, on the one hand, by a good availability of stock cards in the two districts with proportions equal to 100% and 94.1%, respectively, and on the other hand, by the presence of expired stocks in Pete (12.2%). About 79% and 88% of prescribers reported prescribing the basket drug, respectively. These results show that access to priority life-saving medicines for children remains a challenge.