Study aimed to investigate the impact of long-term high ambient temperature (HAT) exposure and dietary antioxidant supplementation (elevated levels and in combination) on nutrient digestibility, metabolism and immune response of pigs. A total of 36 Danbred barrows (65.1 ± 2.81 kg) were allotted to four treatments: Trm1: HAT (28.9 ± 0.9 °C) + control diet (CD); Trm2: HAT + elevated vitamin C and E and Se and Zn; Trm3: HAT + further elevated vitamin C and E and Se and Zn; and Trm4: thermo-neutral ambient temperature (19.5 ± 0.9 °C) + CD. Nutrients (DM, CP, Cfat, CF, CA, GE) and minerals (Ca, P, Na, Zn, Se) digestibility were determined. Plasma metabolite and cytokine concentrations were investigated from the blood samples collected on d 15 and 28. Heat shock proteins (HSP 70 and 90) and tumor necrosis factor-alpha (TNF-α) expressions were investigated from jejunum samples of pigs. HAT did not significantly affect pigs' nutrient digestibility and retention (P > 0.05). However, Trm2 pigs had greater digestibility in terms of DM, CF, Ca, Zn, Se and retention of Ca, Zn, Na, and Se than Trm1 and Trm4 groups. Trm3 pigs had significantly higher (P < 0.05) creatinine concentrations than Trm4 pigs. HAT did not significantly affect the expression of cytokines; however, vitamins and micro-minerals supplementation in the diet significantly (P < 0.05) improved interleukin (IL) 10 expression, reduced TNF-α, and HSP70 expressions. Vitamin and micro-mineral fortified diet can improve pigs' nutrient and mineral digestibility and could alleviate inflammatory response in pigs exposed to HAT.