We examined the influence of reduced hemoglobin concentrations resulting from malarial infection on metabolism and thermoregulation in the Fence Lizard, Sceloporus occidentalis. Malarial infections diminish the oxygen-carrying capacity of the blood, depressing hemoglobin concentrations by as much as 25%. Lizards collected from Oregon were screened for Plasmodium mexicanum. Malaria-infected and uninfected lizards were placed on a temperature-controlled treadmill at preferred body temperature (35°C) and induced to walk at constant speed for 5 min (0.7 m min−1) or sprint maximally to exhaustion (<2 min of activity). Excess oxygen consumption during recovery was over 30% higher in infected lizards when compared to uninfected lizards following similar levels of activity. Malarial infection significantly elevated blood lactate levels following sprint or endurance activity (20 and 36% elevation, respectively) when compared to uninfected lizards. Malarial infection significantly increased preferred body temperature tested in a thermal gradient following sustained activity (2–4°C increase) but had little impact on thermoregulation following exhaustive exercise. There was a strong negative correlation between hemoglobin concentration and postactivity body temperature. Our findings suggest that there are metabolic costs, measured as excess oxygen consumption and thermoregulation disruptions, associated with malaria-induced hemoglobin depression. These results may help explain limited size and reproductive success previously measured in malaria-infected lizards.