Background: Paralympic powerlifting (PP) training is typically intense and causes fatigue and alterations in the immune system. Objective: To analyze whether IBU would affect performance and the immune system after training in PP. Methodology: 10 athletes at the national level (NL) and 10 at the regional level (RL) participated in the study, where force and blood indicators were evaluated after training. The study took place over three weeks: (1) familiarization and (2 and 3) comparison between recovery methods, with ibuprofen or placebo (IBU vs. PLA), 800 mg. In the evaluation of the force, the peak torque (PT), fatigue index (FI), and blood immune system biomarkers were analyzed. The training consisted of five sets of five repetitions with 80% of one maximum repetition (5 × 5, 80% 1RM) on the bench press. Results: The PT at the national level using IBU was higher than with PLA (
p = 0.007, η2p = 0.347), and the FI in the NL was lower with IBU than with PLA (
p = 0.002, η2p = 0.635), and when comparing the use of IBU, the NL showed less fatigue than the regional level (
p = 0.004, η2p = 0.414). Leukocytes, with the use of IBU in the NL group, were greater than in the RL (
p = 0.001, η2p = 0.329). Neutrophils, in the NL with IBU, were greater than in the RL with IBU and PLA (
p = 0.025, η2p = 0.444). Lymphocytes, in NL with IBU were lower than in RL with IBU and PLA (
p = 0.001, η2p = 0.491). Monocytes, in the NL with IBU and PLA, were lower than in the RL with IBU (
p = 0.049, η2p = 0.344). For hemoglobin, hematocrit, and erythrocyte, the NL with IBU and PLA were higher than the RL with IBU and PLA (
p < 0.05). Ammonia, with the use of IBU in the NL, obtained values higher than in the RL (
p = 0.007), and with the use of PLA, the NL was higher than the RL (
p = 0.038, η2p = 0.570). Conclusion: The training level tends to influence the immune system and, combined with the use of the IBU, it tends to improve recovery and the immune system.
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