A study is conducted to determine the anti-inflammatory effects of cocoa and polyphenol-rich cocoa fractions in the dextran sulfate sodium (DSS)-induced mouse model of acute colonic inflammation. Male C57BL/6J mice are treated with dietary cocoa powder, an extractable cocoa polyphenol fraction, or a non-extractable cocoa polyphenol fraction for 2 weeks prior to treatment with 2.5% DSS in the drinking water for 7 days to induce colonic inflammation. Cocoa treatment continues during the DSS period. Cocoa and/or cocoa fractions exacerbate DSS-induced weight loss and fail to mitigate DSS-induced colon shortening but do improve splenomegaly. Cocoa/cocoa fraction treatment fails to mitigate DSS-induced mRNA and protein markers of inflammation. Principal component analysis shows overlap between cocoa or cocoa fraction-treated mice and DSS-induced controls, but separation from mice not treated with DSS. The results suggest cocoa and cocoa polyphenols may not be useful in mitigating acute colonic inflammation.