The adverse influences of elevated ambient temperatures during the summer season on the rabbit industry have received increased global attention. Therefore, this study intended to compare the potential effects of nano-selenium (nano-Se) synthesized by biological (BIO) and chemical (CH) methods on growth performance, carcass variables, serum metabolites, and inflammatory cytokines responses of growing rabbits in the summer season. Two hundred and fifty weaned rabbits (males, 35 days of age) were randomly divided into five treatment groups of 50 rabbits each (each group had five replicates with ten male rabbits). Treatment groups were fed a control diet and four controlled diets supplemented with nano-Se synthesized by biological method (BIO25 and BIO50, with a 25 and 50 mg of nano-Se/kg diet, respectively) and chemical method (CH25 and CH50, with a 25 and 50 mg of nano-Se/kg diet, respectively) for eight weeks. During 11 to 13 weeks of age, a gradual enhancement in live body weight (LBW), feed intake (FI) and feed conversion ratio (FCR) was noticed with BIO25 and BIO50 treatments compared to those in the other groups. The carcass percentage was significantly higher ( < 0.01) for animals fed with BIO25 than the other groups. The other organ functions were significantly higher ( < 0.01) in heat-stressed groups compared to that of nano-Se groups. Increasing the level of only BIO from a 25 to a 50 mg/kg diet gave more improvement in the studied parameters. Additionally, the concentrations of serum urea, triglycerides (TG), and glutamyl transferase (GGT) were lower ( < 0.01) in both treated and untreated groups. Likewise, the supplementation with nano-Se (BIO25, BIO50, or CH25) significantly improved the antioxidant indices and inflammatory cytokines responses as indicated from serum metabolites. Based on the study results, nano-Se especially synthesized by the biological method at diet levels of 25 or 50 mg/kg improved the growth performance, kidney and liver functions, carcass traits, antioxidants indices, and inflammatory cytokines of growing rabbits during thermal stress.