Background <p>Acutely ill children are at risk of receiving unnecessary antibiotic prescriptions, yet within this context, clinical decision support systems (CDSS) have the potential to improve clinicians’ prescribing behaviour. Since the uptake of CDSS is limited, research into the facilitators and barriers to its use and the preferred content and functions is needed to promote its use.</p> Methods <p>Four focus groups were conducted among Belgian general practitioners, paediatricians, and ear/nose/throat physicians. The groups took place in a university building, a regional hospital, and online, and were semi-structured according to the interview guide. We transcribed recordings and performed reflexive thematic analysis. All participants were asked to provide feedback on the final themes.</p> Results <p>Twenty-five physicians participated in the study. The analysis produced four themes: (i) Physicians prefer a pragmatic approach completing the CDSS, with as little additional work as possible; (ii) The comprehensive advice given by the CDSS should be concise, unambiguous, and presented clearly; (iii) The CDSS can reduce diagnostic uncertainty, especially by making physicians aware of alarm symptoms of serious illness; (iv) The scope should be determined beforehand, and implementation should consider reliability and technical barriers. Participants proposed several possibilities for the content and functions of the CDSS, which are informed by their workload, clinical uncertainty, and their emphasis on professional autonomy.</p> Conclusions <p>The results of this study contribute to the development of a user-friendly CDSS for the assessment of acutely ill children in ambulatory care. Physicians prefer a CDSS that is pragmatic to apply and shows clear guidance on diagnostics and disease management, including support to reduce uncertainty regarding illness severity. The implementation of a CDSS plays a pivotal role in enhancing antimicrobial stewardship.</p>