We determined whole-fish total mercury (Hg) concentrations of 40 male and 40 female adult sea lampreys (Petromyzon marinus) captured in the Cheboygan River, a tributary to Lake Huron, during May 2011. In addition, bioenergetics modeling was used to explore the effects of sex-related differences in activity and resting (standard) metabolic rate (SMR) on mercury accumulation. The grand mean for Hg concentrations was 519 ng/g (standard error of the mean = 46 ng/g). On average, males were 16% higher in Hg concentration than females. Bioenergetics modeling results indicated that 14% higher activity and SMR in males would account for this observed sex difference in Hg concentrations. We concluded that the higher Hg concentration in males was most likely due to higher rate of energy expenditure in males, stemming from greater activity and SMR. Our findings have implications for estimating the effects of sea lamprey populations on mercury cycling within ecosystems, as well as for the proposed opening of sea lamprey fisheries. Eventually, our results may prove useful in improving control of sea lamprey, a pest responsible for substantial damage to fisheries in lakes where it is not native.