Purpose: The authors investigated the effect of foot cooling (FC) between sets in a leg press pyramid workout with resistance-trained participants. Methods: A total of 12 resistance-trained men (age = 21.8 [0.6] y; training experience = 1.7 [1] y) performed a pyramid workout, including 4 sets of 85% to 90% 1-repetition maximum leg press exercise to exhaustion with interset FC or noncooling in a repeated-measures crossover design separated by 5 days. The authors immersed the participants’ feet in 10°C water for 2.5 minutes between sets. Results: Two-way repeated-measures analysis of variance revealed that FC elicited significantly higher repetitions and electromyography (EMG) values of the vastus lateralis (simple main effect of condition) than did noncooling (P < .05) in the second (repetitions: 11 [3.5] vs 7.75 [3.2]; EMG: 63.4% [19.4%] vs 54.5% [18.4%]), third (repetitions: 8.9 [3.2] vs 6.4 [2.1]; EMG: 71.5% [17.4%] vs 60.6% [19.4%]), and fourth (repetitions: 7.5 [2.7] vs 5.1 [2.2]; EMG: 75.2% [19.6%] vs 59.3% [23.5%]) sets. The authors also detected a simple main effect of set in the FC and noncooling conditions on repetitions (P < .05) and in the FC condition on the vastus lateralis EMG values. Although the authors observed no time × trial interactions for the rating of perceived exertion, the authors observed main effects on the sets (7.7–9.6 vs 7.9–9.3, P < .05). Conclusions: Interset FC provides an ergogenic effect on a leg press pyramid workout and may offset fatigue, as indicated by higher repetitions and EMG response, without increasing perceived exertion.