Targeted approaches have been widely used to help explain physiological adaptations, but few studies have used non-targeted omics approaches to explore differences between diving marine mammals and terrestrial mammals. A rank comparison of undepleted serum proteins from common bottlenose dolphins (Tursiops truncatus) and pooled normal human serum led to the discovery of 11 proteins that appeared exclusive to dolphin serum. For dolphin proteins that did not match human serum proteins, a second comparison was made with Yorkshire pig (Sus scrofa)serum proteins to determine whether phylogenetic differences in serum proteins could simply explain the differences between dolphin and human. Three out of 11 proteins that were considered unique to the dolphin high abundance serum proteome were ranked within the high abundance pig serum proteome. Compared to the comprehensive human plasma proteome, 5 of 11 serum proteins had a differential rank greater than 200. Major differences exist in the circulating blood proteome of the bottlenose dolphin compared to terrestrial mammals and exploration of these differences in bottlenose dolphins and other marine mammals may identify veiled protective strategies to counter physiological stress.