This study was designed to characterize and evaluate the proteome in plasma samples collected before and after a public swim interaction involving four male (2 to 6 y) aquarium-based bottlenose dolphins (Tursiops truncatus). Blood samples were collected from the tail flukes appoximately 15 min before (n=4 samples) and 15 min after (n=4 samples) the first swim interaction of the day, which was reinforced by a regularly scheduled feeding regimen. Samples were subjected to liquid chromatography-tandem mass spectrometry (LC-MS/MS) as well as conventional clinical biochemistry analysis. Mass spectra data were used to search the NCBI database restricted to Tursiops truncatus which resulted in the identification of 196 unique proteins with a broad range of functional roles based on manual GO analysis. Differential regulation of proteins was based on log2 mean fold change (FC) and statistical probability such that the abundance of lysozyme (FC -1.2036; P<0.058) an immune-related protein and flavin reductase (FC -0.9702; P<0.004) a metabolic-related protein were highest before compared to after the swim interaction. Both proteins decreased by 58 and 52%, respectively.