Blueberries are a rich source of phenylpropanoid-derived phytochemicals, widely studied for their potential health benefits. Of particular interest for colonic health are the lower molecular weight phenolic acids and their derivatives, as these are the predominant phenolic compounds detected in the colon. Blueberries contained a wide variety of phenolic acids, the majority of which (3371.14 ± 422.30 mg/kg compared to 205.06 ± 45.34 mg/kg for the free phenolic acids) were attached to other plant cell-wall components and therefore, likely to become available in the colon. Cytokine-induced stimulation of the inflammatory pathways in colon cells was four-fold up-regulated in the presence of the free phenolic acid fraction. Incubation of the bound phenolic acids with human faecal slurries resulted in qualitative and quantitative differences in the phenolic compounds recovered. The metabolites obtained by incubation with faecal slurries from one volunteer significantly decreased (1.67 ± 0.69 ng/cm3) prostanoid production, whereas an increase (10.78 ± 5.54 ng/cm3) was obtained with faecal slurries from another volunteer. These results suggest that any potential protective effect of blueberry phenolics as anti-inflammatory agents in the colon is a likely result of microbial metabolism. Studies addressing a wide-range of well-characterised human volunteers will be required before such health claims can be fully established.