Healthcare systems in resource-limited nations have been challenged by the shortage of essential medicines. This study explores cefazolin access and uses history in the Ethiopian healthcare delivery system, for possible policy implications. An exploratory qualitative study was conducted from July to August 2021. Semi-structured questions and observation guides were used to extract necessary data from people, documents, and field visits to hospitals, government supply agencies, and pharmaceutical business firms. The data were transcribed, coded, organized into themes, and presented. Cefazoline is the recommended first-line surgical antibiotic prophylaxis (SAP) in the Ethiopian Standard Treatment Guideline (STG) and is included in the national Essential Medicine List (EML). However, it was not available for use in the Ethiopian pharmaceutical markets for years. While the shortage might stem from supply-demand mismatches, multiple unknown issues exist in the background of the shortage. This is evidenced by the removal of cefazolin from the recent government procurement list regardless of the recommendation set in the national EML and STG. This study found a historic shortage of cefazolin in Ethiopian healthcare settings. This implies that the antibiotic availability in the pull market may not reflect required usage at facilities for several reasons including the misalignment of national guidelines and national procurement processes, and miscommunication between pharmacies and clinicians at sites on drug availability. Changing the essential medicines list and/or procurement requests without active review of the supply chain system and prescribing practices at facilities can lead to the elimination of necessary antimicrobial agents from the national public health sector supply.