Heat stress (HS) is a major concern for human health as well as for the swine industry. In 2012, HS resulted in the largest number of weather related human fatalities in the US. Animal production is also compromised as HS leads to poor sow performance, decreased carcass value and increased veterinary costs. However, the molecular effects of HS on skeletal muscle are still unclear. This study aimed to determine the extent to which HS disrupted redox balance and initiated an inflammatory response in oxidative and glycolytic porcine skeletal muscle. Moreover, we quantified the contribution of reduced feed intake to the disruption of redox balance and inflammatory signaling in porcine skeletal muscle. To achieve this, crossbred gilts were subjected to thermoneutral (TN; 20°C) or HS (35°C) conditions for 1, 3 or 7 days. In order to quantify the contribution of reduced feed intake to the HS response, a group of 7 day TN animals were pair fed (PFTN) to the 7 day HS group. One day of HS increased oxidative stress, measured as a 1.5 fold increase in MDA modified proteins in oxidative muscle but not glycolytic muscle. Further, HS significantly increased the activities of catalase and SOD in oxidative muscle. These data indicated that oxidative muscle was more sensitive to HS than glycolytic muscle. Further, inflammatory signaling was not increased as a result of the HS treatment in STR or STW muscle. Also, reduced feed intake did not significantly contribute to increased oxidative injury or inflammatory signaling in porcine skeletal muscle.