Abstract This paper investigates the neural representation of the processes involved in recognizing multi-syllabic words in Spanish asking whether lexical and sublexical processes are reflected in a different neuronal activation pattern. High and low frequency words were presented for lexical decision in two different colors. In the congruent condition the color boundaries matched the limit of the first syllable, whereas in the incongruent condition color boundaries and syllable boundaries did not match. The results revealed robust and dissociable brain activations for lexical frequency and syllable-color congruency but no interaction between the two. We interpreted the greater activation for low relative to high frequency words in the left pre/SMA region, and in the insula/inferior frontal cortex bilaterally to reflect a differential recruitment of lexico-phonological and/or semantic processes. In contrast, we considered two interpretations for the greater deactivation in the precuneus for both lexical frequency and syllable-color congruency words, and in the thalami and a frontal area for syllable-color congruency words only. The deactivations may reflect the differential engagement of semantic processing or may result from the differential allocation of attentional resources. Importantly, while a differential deactivation pattern was observed in the precuneus region for lexicality and syllable-color congruency, BOLD deconvolution revealed a remarkable difference in timing of the two effects with a much earlier deactivation peak for the syllable-color congruency factor. Thus, effects of lexical frequency and syllable-color congruency on brain activation show an important dissociation between lexical and sublexical processes during visual word recognition of multi-syllabic words.