Thyroid hormones (THs) are very lipophilic molecules which require a distribution network for efficient transport in serum. Despite observations that THs function in a wide variety of processes, including aspects of fish development (i.e., flat fish metamorphosis and smoltification), the proteins responsible for TH distribution in fish serum remain poorly studied. We chose to investigate the serum TH distributor proteins (THDPs) in lampreys. As one of only two extant agnathans, data on lamprey THDPs may offer new insights into the evolution of the vertebrate TH distribution network and serum proteins in general. Moreover, lampreys appear to contradict the vertebrate model of an increase in TH concentrations initiating and driving vertebrate metamorphosis. We show for the first time that sea lamprey serum contains at least four THDPs and that their presence in serum is temporally regulated throughout the life cycle. The albumin, glycoprotein AS is the dominant THDP present in the sera of larval and metamorphosing sea lamprey. In stage seven of metamorphosis, three additional THDPs appear, including the albumin, glycoprotein SDS-1; the glycolipoprotein CB-III; and an unidentified low molecular weight protein temporarily named Spot-5. The sera of parasitic and upstream migrant sea lampreys lack AS; their serum THDPs are SDS-1, CB-III, and Spot-5. Our data indicate that despite the change in type and number of THDPs, the overall total TH binding capacity of sea lamprey serum remains fairly stable until stage 7 of metamorphosis when a only modest decrease in total binding capacity is observed. Collectively these data indicate that the decline in serum TH concentrations observed during lamprey metamorphosis is not a consequence of a reduction in the distribution and storage capacity of the serum.