Exposure of pigs to sudden increases in ambient temperature (AT), causing heat stress (HS) provokes cellular and molecular changes to cope with HS and maintain homeostasis. Abundance of mRNA coding for heat shock protein 70 kDa (HSP70) involved in the folding of proteins during heat stress, uncoupling protein 3 (UCP3) involved in heat generating in mitochondria, and cytochrome p450 (Cp450) involved in redox equilibrium, is affected in animals under acute HS. But it is not clear whether those alterations are maintained in pigs with chronic exposure to HS. An experiment was conducted with 18 pigs (30–35 kg BW) to analyze the effect of chronic HS on mRNA expression of HSP70, UCP3, and Cp450. There were 3 treatments: 1) pigs housed inside an AT controlled room (24 ± 2°C) and fed ad libitum (TNL), 2) as in 1 but feed restricted (TNR), 3) pigs housed under natural HS conditions (27.1 to 39.6°C, average 33.3°C). Feed intake in HS pigs was restricted to 95% of ad libitum intake, and that of TNR pigs was similar to HS pigs. Body temperature (BT) was recorded every 15 min with a device implanted under the skin of 4 pigs per treatment. At the end of the 21-d study, all pigs were killed and samples of liver, and longissimus (LM) and semitendinosus (SM) muscles were collected to analyze the mRNA expression of HSP70, UCP3 and Cp450. The BT of TNL, TNR, and HS pigs was 38.4, 37.7 and 39.0°C, respectively. It was higher in HS pigs compared with TNL and TNR (P < 0.05). Expression values (×10⁻⁴) for HSP70 in TNL, TNR, and HS pigs were liver, 2.03, 4.08, 7.66; LM, 2.47, 5.2, 4.69; SM, 2.10, 2.31, 2.23, respectively; for UCP3 were LD, 4.58, 4.92, 3.57; SM, 3.46, 2.42, 6.04. Expression values (×10⁻³) for Cp450 in liver were 3.59, 1.77, 1.68. Chronic HS did not affect the expression of HSP, UCP3 or Cp450 in pigs. Although BT of pigs exposed to chronic HS remains higher than in TN pigs, the lack of effect on gene expression may suggest that pigs became acclimated at or before 21 d of natural exposure to HS.