This study observed the pigs' performance and physiological responses to heat stress (HS) and dietary antioxidants supplementation. Growth performance, rectal and skin temperature, blood biochemical parameters (glucose, uric acid, urea, and creatinine), and markers for electrolyte balance (plasma sodium, potassium, and chloride concentration) were measured from 36 DanBred finishing pigs, while meat quality, nutrient and mineral digestibility (faecal and ileal), retention, and expression of pro and anti-inflammatory cytokines were measured on 24 pigs weighing 65 ± 2.81kg at the start of the trial. The pigs were exposed to four different treatments TC: TN + C: thermo-neutral ambient temperature (19.5 ± 0.9 °C, RH- 85.9 ± 7.3%) and basal or control diet (NRC, 2012), HC: HS + C: heat stress (28.9 ± 0.9 °C, RH- 60.4 ± 4.3 %) + control diet, HT1: HS + T1 (elevated diet 1: single dose supplementation of vitamin C and E and Se and Zn content), and HT2: HS + T2 (elevated diet 2: double dose supplementation of vitamin C and E and Se and Zn content) (the variables were temperature and diet). The pigs' rectal temperature, growth performance and meat quality were not affected (P > 0.05) by HS and elevated levels of dietary antioxidants. However, the skin temperature from the ear base, the middle of the ear and the back was affected by HS (P < 0.05). The capability of antioxidants to reduce the pigs' skin temperature was observed on the measurement from the pigs' back, where HT1 and HT2 pigs had lower (P < 0.05) skin temperature as compared to pigs in the HC group. At day 7 of exposure, the plasma creatinine level was significantly lower in thermal comfort pigs (TC) fed a control diet compared to HT2. At day 21 of exposure, however, the plasma concentration levels were similar. Prolonged HS exposure elevated the plasma concentration of sodium, and regardless of its duration, pigs' plasma chloride concentration was reduced (P < 0.05) by the said stressor, indicating an imbalance which was mitigated by high dietary antioxidant supplementation (T2). HS did not affect the pigs' nutrient digestibility and retention. Nevertheless, dry matter (DM) and crude protein (CP) digestibility were higher in HT1 than TC (P < 0.05), and crude fiber (CF) digestibility was lower in HC and TC groups (P < 0.05) than in HT1 and HT2 groups. While the digestibility of crude fat (Cfat), energy, and crude ash (CA) was not affected (P > 0.05). It was observed, that calcium (Ca) digestibility was higher in HT1 than TC, while zinc (Zn) and selenium (Se) digestibility was higher in HT1 and HT2 than HC and TC (P < 0.05). The retention of Ca, Na, Zn, and Se was higher (P <0.05) in HT1 and HT2 groups than in HC and TC groups. Supplementation of dietary antioxidants at a single dose (T1) in the diet improved (P < 0.05) the CA and CP and some minerals (Zn, Se, and Na) ileal digestibility of pigs despite the HS challenge. HS did not significantly affect (P > 0.05) the expression of cytokines and heat shock proteins (HSPs) in pigs. However, supplementation of vitamins and micro-minerals at the T1 level improved (P < 0.05) the expression of anti-inflammatory cytokine (IL-10) and reduced the expression of pro-inflammatory cytokine (TNF-α) in HT1 and HT2 (P < 0.05) pigs compared to HC group. The mRNA expression of HSP 70 was also reduced (P < 0.05) in pigs fed the T2 diet (HT2 group). In conclusion, the genotype used in the experiment was resilient to most of the harmful effect of HS regarding to the parameters studied. Nonetheless, dietary antioxidants at the T1 level (Vitamins C (150 mg/kg) and E (41 mg/kg) and micro-minerals (Zn (100 mg/kg) and Se (0.21 mg/kg)) can improve nutrient and mineral digestibility and retention despite HS challenge. T2 (Vitamins C (300 mg/kg) and E (71 mg/kg) and micro-minerals (Zn (150 mg/kg) and Se (0.26 mg/kg) supplementation, on the other hand, could improve electrolyte concentration. Supplementation with T1 and T2 levels could reduce inflammatory responses and cell damage in pigs exposed to HS conditions.