Water deprivation is an important limiting factor in the productivity of crops like coffee. In addition to transcription factors (TFs) and small non-coding RNAs, transcriptional memory seems to act in gene expression modulation during plant drought response. Here, a RNA-Seq approach was used to investigate the drought responses of Coffea canephora clones 109 and 120, which are respectively sensitive and tolerant to drought. Illumina sequencing allowed us to identify differentially expressed genes (DEG) in the tolerant (826) and sensitive (135) clones and their enriched categories. Our results indicate that the sensitive clone may trigger anoxidative stress response, possibly leading to programmed cell death, when exposed to multiple drought epi-sodes. The acclimation of tolerant plants, on the other hand, seems to involve antioxidant secondary metabolismand the ABA response. Most importantly, 49 memory genes were identified in the tolerant clone. They were mainly linked to the ABA pathway, protein folding and biotic stress. Small RNA profiling also identified regulatory microRNAs in coffee leaves, including hundreds of putative novel ones. Our findings strongly suggest that transcriptional memory modulates the expression of drought-responsive genes and contributes to drought tolerance in C. canephora.