Background <p>Malaria is a significant public health concern, particularly in sub-Saharan Africa, where it causes considerable morbidity and mortality. Severe malaria is a major cause of mortality among children under five, contributing to Uganda’s high malaria mortality burden. Effective case management of severe malaria is crucial which should be guided by the Uganda clinical guidelines adopted from the World Health Organization. This study explored the barriers and facilitators to healthcare providers’ adherence to severe malaria treatment guidelines in children at Mbale Regional Referral hospital, Uganda.</p> Materials and methods <p>A qualitative descriptive approach was carried out at Mbale Regional Referral Hospital, eastern Uganda. A total of 21 healthcare providers (doctors, nurses, pharmacists; Laboratory technicians; Blood Bank health workers; and clinical officers) were purposively recruited during the study period. Data was collected through key informant interviews, audio recorded, and analyzed using thematic analysis using Braun and Clark’s approach. Adherence to the Lincoln and Gubba principles of credibility, conformability, transferability, and dependability was ensured. Data was presented in tables and narratives. Avis Donabedian model was employed to explore the facilitators and barriers to adherence to the severe malaria management guideline.</p> Results <p>The study identified key facilitators under three themes: Structure (availability of resources, drugs, and training); Process (optimal working conditions, manageable workloads, and use of monitoring tools like yellow stickers); and Patient-related factors (caretaker cooperation, effective communication, and trust-building). Barriers included structure resource constraints, staffing and work load issues; process, delayed referrals, delays in the lab, limited working hours in the lab and pharmacy, low CMEs attendance among nurses; patient related factors like patient financial limitations and poor patient cooperation.</p> Conclusion <p>This study identified facilitators and barriers to adherence to severe malaria management guidelines in children under five. The barriers and facilitators emerged in terms of structural, processes, patient characteristics and outcome. Addressing resource shortages and improving staffing and workload conditions are crucial for better adherence. Enhancing patient education and strengthening health system infrastructure are also essential for ensuring timely and effective care.</p>