The first step, for the establishment of a breeding program based on marker-assisted selection for drought tolerance on coffee, is the identification of molecular markers associated with this trait. This work reports on preliminary results of the effect of drought stress on the expression of the small subunit (RBCS) of the enzyme Ribulose 1,5-Bisphosphate Carboxylase (RUBISCO). Different contigs encoding for this enzyme could be identified by analyzing the Coffee Genome Database. Specific primers designed based on these contig sequences were used for qPCR experiments and the results indicated that RBCS gene expression in leaves of C. canephora and C. arabica is down regulated by drought stress. On the other hand, proteomic analyses by 2DE have shown that the total expression of RBCS increases upon drought stress and new isoforms of this enzyme could specifically be observed under these conditions. These results indicate that a drought stress affects gene expression of important components of the photosynthetic apparatus of coffee plants and the appearance of new isoforms and/or post-transduction modifications of RBCS might represent an adaptive response of coffee plants to water limitation.