Cannabidiol (CBD) is a dietary supplement with numerous purported health benefits and an expanding commercial market. Commercially available CBD preparations range from tinctures, oils, and powders, to foods and beverages. Despite widespread use, information regarding bioavailability of these formulations is limited. The purpose of this study was to test the bioavailability of two oral formulations of CBD in humans and explore their potential acute anti‐inflammatory activity. We conducted a pilot randomized, parallel arm, double‐blind study in 10 healthy adults to determine differences in pharmacokinetics of commercially available water and lipid‐soluble CBD powders. Participants consumed a single 30 mg dose, which is within the range of typical commercial supplement doses, and blood samples were collected over 6 hr and analyzed for CBD concentrations. Peripheral blood mononuclear cells (PBMCs) were collected at baseline and T = 90 min, cultured and stimulated with bacterial lipopolysaccharide (LPS) to induce an inflammatory response. Cell supernatants were assayed for IL‐10 and TNF, markers of inflammation, using enzyme‐linked immunosorbent assays. The water‐soluble powder had Cmax = 2.82 ng/ml, Tmax = 90 min, and was approximately ×4.5 more bioavailable than the lipid‐soluble form. TNF was decreased in LPS‐stimulated PBMCs collected 90 min after CBD exposure relative to cells collected at baseline. This study provides pilot data for designing and powering future studies to establish the anti‐inflammatory potential and bioavailability of a larger variety of commercial CBD products consumed by humans.