UNLABELLED: Compounding oral liquids is a common practice in pediatrics given the scarcity of medications suitable for children. However, compounded products are unlicensed. Their safety, effectiveness and quality are not assessed by regulatory agencies. Then, the assessment of critical characteristics of compounded medications relies on compounding pharmacies. Since the osmolality of oral liquids may contribute to gastrointestinal complications, this study aimed to evaluate the osmolality of compounded oral liquid medications. The osmolality of compounded liquid medications listed in the formulary of our institution was measured. The source of the active pharmaceutical ingredient and the vehicle of each compounded medication were collected. Results showed that 61% of the 28 compounded medications exceeded the recommended threshold of 450 mOsm/kg. The primary determinant of osmolality was found to be the vehicle used in compounding, with commercial vehicles being associated with higher osmolality values. The active pharmaceutical ingredient had minimal influence on the osmolality. CONCLUSION: These findings underscore the importance of the vehicle in the osmolality of compounded oral liquids. Careful selection of compounding vehicles is required to minimize the risks associated with high-osmolality medications, especially for vulnerable populations such as enterally fed neonates. The systematic assessment of osmolality of compound medication would support the implementation of strategies to mitigate the risks associated with high osmolality and improve the safety of compounded pediatric medications. WHAT IS KNOWN: • Compounded oral liquid medications are widely used in pediatrics due to the limited availability of commercial pediatric formulations. • High osmolality in liquid oral medications may contribute to adverse effects. WHAT IS NEW: • This study highlighted the significant impact of the compounding vehicle on the osmolality of compounded oral liquid medications. • Careful selection of compounding vehicles is important, especially for vulnerable children.