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The physicochemical and biochemical changes during the fermentation of four clones and two native varieties of <i>Theobroma cacao</i> L. were studied. Fermentation was performed in traditional wood cubes. During fermentation, the cotyledon pH decreased, and the temperature increased to more than 10 °C above the ambient temperature (47 °C). The fermentation index (FI) increased in the clones C1, C4, C8, C9, and Guayaquil (G) to close to one at 120 h of fermentation. For the FI of the cocoa Criollo (Cr), a value of 2.5 was proposed according to the spectrophotometric scan performance. The total polyphenol content increased in all the samples from 21 (C8) to 70 (Cr) % in a comparison of the TPC at T0 and T120, respectively. The total flavonoid content increased from 16 (C8) to 51% in Guayaquil (G) during the fermentation period. In the case of the methylxanthines, such as theobromine and caffeine, both quantities decreased. The theobromine content decreased in all the samples from 6 (G) to 31% (C8). The caffeine content decreased in all the samples from 3% in Cr to 25% in C1 and G after fermentation. The antioxidant capability did not change after 120 h of fermentation, and the amount of methylxanthines did not affect the antioxidant potential of the fermented cocoa. The FTIR scan of the fat-free cocoa showed significant differences between the unfermented and fermented beans, and several peaks assigned to carbohydrates and proteins decreased.