Determining the consequences of body size and body temperature (T_b) variation is critical to understanding many aspects of snake ecology, because size and temperature play such important roles in the biology of ectotherms. Here, we investigate the effects of body size and temperature variation on the energetics of the largest species of rattlesnake, the Eastern Diamondback Rattlesnake (Crotalus adamanteus). Specifically, we measured oxygen consumption to estimate the standard metabolic rate (SMR) of five C. adamanteus (mass range 800–4980 g) at 5-degree increments from 5–35 C. A multiple regression model indicated that SMR increased with body size and temperature. Q₁₀s were generally high (range 1.82–4.20) compared to other squamates but were similar to the high values calculated for other large rattlesnakes. An energy balance model for C. adamanteus predicted that as T_b increases, so must prey consumption to meet annual SMR energy demands. Thus, T_b variation likely affects patterns of energy acquisition and use and, in turn, influences processes such as growth and reproduction.