Background: Coenzyme Q10 (CoQ10) is a naturally occurring compound that plays a fundamental role in cellular bioenergetics and is an effective antioxidant. Numerous health benefits of CoQ10 supplementation have been reported, resulting in growing demands for its use in fortifying food. Due to its insolubility in water, the enrichment of most food products is not easily achievable and its in vivo bioavailability is known to be poor. Water solubility was increased significantly with the use of an inclusion complex with β-cyclodextrin. This complex is widely used as Q10Vital® in the food industry, while its in vivo absorption in humans has not previously been studied. Methods: A randomized three-period crossover clinical trial was therefore performed in which a single dose of CoQ10 was administered orally to healthy human subjects. The pharmacokinetic parameters of two forms of the novel CoQ10 material were determined and compared to soft-gel capsules with CoQ10 in soybean oil that acted as a reference. Results: The mean increase of CoQ10 plasma concentrations after dosing with Q10Vital® forms was determined to be over the reference formulation and the area under the curve values, extrapolated to infinity (AUCinf), were also higher with the tested forms; statistically significant 120 and 79% increases over the reference were calculated for the Q10Vital® liquid and powder, respectively. Conclusions: The study revealed that the absorption and bioavailability of CoQ10 in the novel formulations are significantly increased, probably due to the enhanced water solubility.