This study aims to compare the electron spin resonance (ESR) spectra emitted by human blood loaded with either ascorbyl-6-palmitate (AP), a lipid-soluble derivative of ascorbic acid (AA), or with AA. Whole blood of a healthy male individual was equilibrated with equimolar concentrations of AP and AA of 200, 400, and 800 μmol/l. The intensity of the ESR signal, expressed as the peak-to-peak amplitude, reflects the amount of unpaired spins that are created due to the reducing action of AA and is proportional, in relative terms, to the amount of the ascorbyl radical formed. We found that the blood with AP emitted an ESR signal whose singlet shape, width, and location precisely correlate with the known characteristics of the ascorbyl radical in vitro. The signal magnitude increased linearly with increasing concentrations of AP and was similar to that of AA. We conclude that AP is biologically active, as it generates the ascorbyl radical, an action that also underlies the scavenging process by ascorbic acid. To this end, ascorbyl-6-palmitate might have potential advantages, due to its ability to penetrate biomembranes and to act at the lipid-related molecular target sites.