Characterizing the physiological response to prolonged cold exposure is essential for understanding the maintenance of long-term energy balance. As part of their natural life cycle, temperate ectotherms are often exposed to seasonal variation in temperatures, including extended periods of cold well below their activity range. Relatively little is known about variation in physiological responses as vertebrate ectotherms enter and exit brumation in response to sustained cold temperatures. We tested the influence of temperature on physiology before, during, and after a simulated brumation in the checkered garter snake (Thamnophis marcianus), a widespread ectothermic vertebrate. We tested for the relative effect of immediate temperature and physiological context (entering or exiting brumation) on hormones regulating energy balance, indicators of energy availability, and resting metabolic rate (V̇" role="presentation" style="box-sizing: border-box; margin: 0px; padding: 0px; display: inline-block; line-height: normal; font-size: 16.2px; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; position: relative;">V̇O2). Plasma corticosterone, glucose, and insulin, as well as immune cell heterophil: lymphocyte ratios responded to temperature, though they did so with different thermal response curves. Thermal sensitivity varied both among and within physiological measures depending on whether animals were going into or coming out of brumation. Additionally, V̇" role="presentation" style="box-sizing: border-box; margin: 0px; padding: 0px; display: inline-block; line-height: normal; font-size: 16.2px; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; position: relative;">V̇O2 was regulated beyond simple temperature-dependence, whereby post-brumation measures were depressed relative to pre-brumation measures at the same temperature. This pattern was characterized by a change in the temperature coefficient (Q10), with a larger pre-brumation Q10, suggesting reduced thermal sensitivity of metabolic rate following a period of extended cold exposure. The integrated physiological response presented here demonstrates not only temperature dependence across physiological axes, but seasonal variation in thermal responsiveness. Our results suggest that energy allocation decisions and hormonal regulation of underlying processes promote differing levels of thermal sensitivity when entering or exiting brumation.