This study investigated the effects of ischemic preconditioning (IPC) on performance during highintensity resistance exercise (RE) sessions, as well as the additional effects of inter-set palm cooling (PC) and the potential underlying mechanisms. Twelve resistance-trained men participated in three RE sessions in a randomized order: (1) IPC followed by RE with inter-set PC (15°C for 2.5 minutes), (2) IPC followed by RE, (3) SHAM followed by RE. IPC involved four cycles of 5-minute ischemia/5-minute reperfusion at 220 mmHg on the upper arm, whereas SHAM involved 20 mmHg with a pneumatic cuff. The RE protocol included three sets to exhaustion, consisting of six exercises at 85% of one-repetition maximum. Multiple perceptual parameters were assessed during RE, and blood samples were obtained both before and after four cycles of ischemia/reperfusion as well as after RE. The results indicated that compared with SHAM, IPC significantly increased the total work volume (∆ = 2.6%); the total number of repetitions (∆ = 4.3%); the number of repetitions in specific exercises; and the levels of several arousal indicators, such as norepinephrine levels before RE and arousal level (assessed using the Felt Arousal Scale) during RE (p < 0.05). The IPC + PC combination further outperformed SHAM alone in most parameters (p < 0.05). However, fatigue indicators (rating of perceived exertion and lactate level) did not differ significantly across the protocols. In conclusion, this study suggest that IPC enhances high-intensity RE performance, potentially through increased arousal levels, with PC augmenting exercise performance by amplifying the arousal response.