Africa's Gulf of Guinea, a major nesting ground for the critically endangered Leatherback Sea Turtle (Dermochelys coriacea), is experiencing rapid economic development. This study reports on the plasma biochemistry and packed cell volume (PCV) of turtles (55 samples collected from 23 individuals) nesting on Playa Moaba, Bioko Island, Equatorial Guinea. Because energy reserves and other resources in an individual are finite and turtles may not feed between nesting episodes, decreasing trends are expected in certain plasma biochemical concentrations and PCV values, as well as maternal investment in reproductive output (clutch size and egg mass). Calcium, potassium, sodium, phosphorous, plasma total protein, albumin, and globulin concentrations changed significantly with increasing number of nesting events, but remained within reported intervals in reptiles. Packed cell volume decreased significantly as the number of nesting events per individual increased. Although clutch size did not change, egg mass decreased significantly with increasing number of nesting events. The observed trends may be due to depletion of energy reserves and other resources during reproduction in a possible fasting state, and to the associated physiological stress.