Background <p>The purpose of this study was to investigate effects of caffeinated chewing gum-induced sympathetic activation and diuretic effect on the rapid rate of weight loss in bodybuilders.</p> Methods <p>Fourteen current elite natural bodybuilding athletes (age: 26 ± 7 years old; BMI: 26.9 ± 7.1&#xa0;kg/m²; muscle mass: 40.4 ± 7.1&#xa0;kg; %body fat: 15.5 ± 4.4%) were included as participants. After confirming the specific gravity of the urine, the participants chewing either caffeinate Gum containing 3&#xa0;mg/kg of caffeine (CAF trial) or placebo gum without containing caffeine (PL trial) for 10&#xa0;min, with a randomized, double-blind, cross-over design. Following a 15-minute period of rest, the participants undergo a weight reduction process by engaging in cycling on a bicycle with an adjustable resistance level. The cycling is performed until the participant has experienced a dehydration state, resulting in a weight reduction of 2% of their initial body weight. Record time, heart rate, heart rate variability (HRV) urination volume and energy expenditure from exercise to completion of dehydration.</p> Results <p>The urination volume (<i>P</i> = 0.040) and sympathetic activation were significantly higher in the CAF trial than in the PL trial during dehydration exercise (<i>P</i> &lt; 0.05). Time to dehydration (<i>P</i> = 0.024) and the rating of perceived exertion (RPE) score during exercise were significantly lower in the CAF trial than in the PL trial. There were no significant differences in heart rate and energy expenditure during dehydration exercise between the two trials (<i>P</i> &lt; 0.05).</p> Conclusions <p>This study found that chewing caffeinated gum increased sympathetic nerve activity and accelerated dehydration in bodybuilders.</p> Trial registration <p>This study was registered in ClinicalTrials.gov (Date: 04/08/2024; ID “NCT06431035”; <a href="https://register.clinicaltrials.gov">https://register.clinicaltrials.gov</a>).</p>