Heat stress and immune challenges negatively impact nutrient allocation and metabolism in swine, especially due to elevated heat load. In order to assess the effects of heat stress during porcine reproductive and respiratory syndrome virus (PRRSV) infection on metabolism, 9-week old crossbred barrows were individually housed, fed ad libitum, divided into four treatments: thermo-neutral (TN), thermo-neutral PRRSV infected (TP), heat stress (HS), and heat stress PRRSV infected (HP), and subjected to two experimental phases. Phase one occurred in TN conditions (22°C) where half the animals were infected with PRRS virus (n=12), while the other half (n=11) remained uninfected. Phase two began, after 10 days with half of the uninfected (n=6) and infected groups (n=6) transported to heated rooms (35°C) for three days of continuous heat, while the rest remained in TN conditions. Blood samples were collected prior to each phase and at trial completion before sacrifice. PPRS viral load indicated only infected animals were infected. Individual rectal temperature (Tr), respiration rates (RR), and feed intakes (FI) were determined daily. Pigs exposed to either challenge had an increased Tr, (P < 0.0001) whereas RR increased (P < 0.0001) with heat stress, compared to TN. Average daily gain (ADG) and body weight (BW) decreased with challenges compared to TN, with the greatest loss to HP pigs. Markers of muscle degradation such as creatine kinase, creatinine, and urea nitrogen were elevated during challenges. Blood glucose levels tended to decrease in HS pigs. Heat stress tended to decrease WBC and lymphocytes and increase monocytes and eosinophils during HS. However, neutrophils were significantly increased (P < 0.01) during HP. Metabolic flexibility tended to decrease in PRRS infected pigs as well as HS pigs. Fatty acid oxidation measured by CO2 production decreased in HP pigs. Taken together, these data demonstrate the additive effects of the HP challenge compared to either PRRSV or heat stress alone.