To investigate functional divergence of gene duplicates, we examined the protein-protein interactions and coexistence in complexes of paralogs resulting from an ancient whole-genome duplication in yeast. Strikingly, half the surveyed paralog pairs were found to be co-clustered in protein complexes, and were more conserved and highly expressed than non-co-clustered paralogs; however, their discordant expression patterns and conservation rates indicate differential regulation of subfunctionalized paralogs. These results highlight the value of protein complex membership in studying functional divergence among gene duplicates.