The common cold is one of the most frequently encountered infectious diseases in humans and, despite the modest severity in most cases; it presents a significant economic burden upon society and individuals. ColdZyme^® Mouth Spray (ColdZyme^®, Enzymatica AB, Lund, Sweden) is a mouth spray intended to reduce the probability of catching a cold and can also help shorten the duration of a cold if used at an early stage of the infection, by forming a barrier on the oropharyngeal mucous membrane. This study evaluated the effect of ColdZyme^® on common cold related sick-leave in preschool (kindergarten) staff. Fifteen preschool staff members were evaluated over a 6-month period and ColdZyme^® was used according to instructions. Sick-leave days were recorded and compared to historical data. The number of average sick leave days decreased during the period from 7.4 days to 4.1 days (p = 0.04). It is notable that, if occurring, the majority of subjects perceived a common cold infection as milder than usual. Conclusion: Using ColdZyme^® to apply a barrier to the pharyngeal mucous membrane may be an easy and practical way to prevent or reduce infections and corresponding sick leave in personnel from the preschool environment.