Yogic breathing (YB) has been suggested to reduce stress and blood pressure and increase cognitive processes. However, alterations after YB at the molecular level are not well established. Twenty healthy volunteers were randomized into two groups (N = 10 per group): YB or attention controls (AC). The YB group performed two YB exercises, each for ten minutes, for a total of twenty minutes in a single session. AC group read a text of their choice for 20 minutes. Saliva was collected at baseline and at 5, 10, 15, and 20 minutes. Using Mass Spectrometry (MS), we initially found that 22 proteins were differentially expressed and then validated deleted in malignant brain tumor-1 (DMBT1) and Ig lambda-2 chain C region (IGLC2) using Western Blotting. DMBT1 was elevated in 7 of YB group by 10-fold and 11-fold at 10 and 15 minutes, respectively, whereas it was undetectable in the time-matched AC group (P < 0.05). There was a significant interaction between groups and time assessed by two-way ANOVA (P < 0.001). IGLC2 also showed a significant increase in YB group as measured by Western Blotting. These data are the first to demonstrate the feasibility of stimulating and detecting salivary protein biomarkers in response to an acute Yoga exercise. This trial is registered with ClincalTrials.gov NCT02108769.