Lamprey (Petromyontiformes) are the oldest extant family in the vertebrate lineage, providing a unique phylogenetic position for studies on vertebrate evolution. As a basal vertebrate, sea lamprey (Petromyzon marinus) is an important species to understand evolution and comparative physiological mechanisms, including osmoregulation and appetite regulation. Sea lamprey has anadromous (native to the Atlantic Ocean) and landlocked (invasive in the Laurentian Great Lakes in North America) populations. In both populations of sea lamprey, the blind filter-feeding freshwater (FW) larvae burrow in stream sediments for until undergoing a hormonal-driven metamorphosis. During this phase, sea lamprey do not feed as major morphological and physiological changes occur, including the development of salinity tolerance and parasitic anatomy. After metamorphosis, sea lamprey migrate to the ocean (anadromous), or FW lakes (landlocked) where they attach to a host and feed parasitically. After a rapid growth phase, adults return to FW streams to spawn and die. In this thesis, I examine the osmoregulation and appetite regulation of sea lamprey. In Chapter 2, I describe the osmoregulatory and ionoregulatory capacities of one anadromous (Connecticut River) and three landlocked (Lake Champlain, Hammond Bay, and Thunder Bay) populations exposed to FW or seawater (SW) over two weeks (Chapter 2). In Chapter 3, I functionally characterize a FW ion uptake transporter, the Na+:Cl- cotransporter (NCC) in the gill of sea lamprey across life stages and salinity environments. In Chapter 4, I compare physiological and hormonal differences between feeding and non-feeding parasitic juvenile sea lamprey, using specific growth rate and plasma triglycerides as confirmation for feeding behavior., I describe differences in appetite- and feeding- regulating hormones in the first feeding following metamorphosis. Collectively, this dissertation contributes to conservation and management practices for native and invasive sea lamprey, and it contributes to the knowledge of osmoregulation and appetite regulation in the context of vertebrate evolution.