Despite well‐studied clinical manifestations, intracellular mechanisms of prolonged hyperthermic injury remain unclear, especially in skeletal muscle. Given muscle's large potential to impact systemic inflammation and metabolism, the response of muscle cells to heat‐mediated injury warrants further investigation. We have previously reported increased activation of NF‐κB signaling and increased NF‐κB and AP‐1‐driven transcripts in oxidative skeletal muscle following 12 h of heat stress. The purpose of this investigation was to examine early heat stress‐induced inflammatory signaling in skeletal muscle. We hypothesized that heat stress would increase NF‐κB and AP‐1 signaling in oxidative skeletal muscle. To address this hypothesis, 32 gilts were randomly assigned to one of four treatment groups (n = 8/group): control (0 h: 21°C) or exposed to heat stress conditions (37°C) for 2 h (n = 8), 4 h (n = 8), or 6 h (n = 8). Immediately following environmental exposure pigs were euthanized and the red portion of the semitendinosus muscle (STR) was harvested. We found evidence of NF‐κB pathway activation as indicated by increased protein abundance of NF‐κB activator IKK‐α following 4 h and increased total NF‐κB protein abundance following 6 h of heat stress. Heat stress also stimulated AP‐1 signaling as AP‐1 protein abundance was increased in nuclear fractions following 4 h of heat stress. Interleukin‐6 protein abundance and activation of the JAK/STAT pathway were decreased in heat stressed muscle. These data indicate that heat stress activated inflammatory signaling in the porcine STR muscle via the AP‐1 pathway and early activation of the NF‐κB pathway.