Liquid biopsy utilizing cell-free DNA (cfDNA) has become an emergent field of study for cancer screening and monitoring. While blood-based liquid biopsy has been investigated extensively, there are advantages to using other body fluids. Using saliva is noninvasive, repeatable, and it may be enriched with cfDNA from certain cancer types. However, the lack of standardization in the pre-analytical phase of saliva-based testing is a concern. In this study, we evaluated pre-analytical variables that impact cfDNA stability in saliva specimens. Using saliva from healthy individuals, we tested different collection devices and preservatives and their effects on saliva cfDNA recovery and stability. Novosanis’s UAS preservative helped stabilize cfDNA at room temperature for up to one week. Our study provides useful information for further improvements in saliva collection devices and preservatives.