For over a century, hypotheses regarding the primary functional utility of snake venoms have been debated in literature. Researchers have speculated that the development of venom delivery systems has been a key innovation leading to the evolutionary radiation of venomous snakes over the past 25–30 million years. Interestingly, little is known about the energetic requirements involved in producing venoms in these animals. Here I examined the metabolic cost associated with venom production in three species of North American pitvipers. Immediately following venom extraction, snakes demonstrated an 11% increase in resting metabolic rates during the first 72 h of venom replenishment; this metabolic increase was apparently a result of metabolic costs involved with venom production and was an order of magnitude greater than that predicted for producing an identical mass of mixed body growth. Extracted liquid venom yield of snakes was allometrically correlated with snake body mass (4.77W0.60) and had mean moisture content of 70.9%. Venom yields (wet or dry) were not correlated with the magnitude of the metabolic increase measured during the first 72 h of venom replenishment, suggesting the cost of venom replenishment is independent of extracted mass. The significant post-extraction metabolic increases measured in these snakes support existing hypotheses about the metabolic cost of venom production and may help explain why these animals meter their venom conservatively.