PURPOSE Creatine (Cr), a widely used ergogenic aid, was studied for its effect on acute changes in plasma volume, electrolytes, and mineral balance. Coaches, trainers, professional sports teams, and physicians have raised concerns regarding the potential heath risks associated with oral creatine supplementation. Numerous anecdotal reports suggest that Cr supplementation alters the intracellular/extracellular electrolyte balance of skeletal muscle tissue. This may lead to hyperexcitability of motor neurons causing irregular firing patterns of high-frequency, high-amplitude potentials, that in turn leads to an increase in skeletal muscle cramping and possible tearing. METHODS Using a randomized double-blind design, 26 subjects ingested either 20 g·d−1 of creatine monohydrate (CR1) (n=7), 40 g·d−1 of creatine monohydrate (CR2) (n=10), or a placebo (PL) (n=9) for 3-d. RESULTS After supplementation there were significant changes (p ≤ 0.05) in plasma volume (Δ PV) between the placebo and both Cr groups on all three days (day 1-AM/day 1-PM, PL: 4.3 ± 0.9; CR1: −1.0 ± 1.0; CR2: −0.9 ± 1.0%), (day 1-PM/day 2-AM, PL: 1.2 ± 1.7; CR1: −2.7 ± 1.6; CR2: −3.6 ± 1.3%), (day 2-AM/day 2-PM, PL: 4.9 ± 2.6; CR1: −0.6 ± 1.6; CR2: −2.5 ± 1.6%), (day 2-PM/day 3-AM, PL: 3.9 ± 1.6; CR1: −3.2 ± 1.1; CR2: −4.8 ± 1.4%), (day 3-AM/day 3-PM, PL: 6.6 ± 2.7; CR1: 0.8 ± 2.5; CR2: −2.7 ± 1.8%). There were no significant differences, within or between groups, in serum electrolytes (Na, K, Cl), magnesium, hemoglobin, hematocrit, or osmolality for any day. CONCLUSIONS This is the first reported study investigating Cr supplementation's effect on the acute Δ PV, electrolytes, and mineral balance. These results suggest that a 3-d loading dose of 20 g·d−1 or 40 g·d−1 of Cr significantly reduce plasma volume with the 20 g·d−1 dose returning back to positive levels on day 3 while the 40 g·d−1 dose remains reduced on all 3 days. However, serum electrolyte, mineral balance, and osmolality remain unaffected.