Frosty pod rot (FPR), caused by Moniliophthora roreri (MR), is one of the most important diseases of cacao, causing losses of up to 90% in areas where it is present. A limited number of resistant clones have been identified, but additional sources of disease resistance are being sought by breeding programs. RNA sequencing was used to identify differences in constitutive (mock-inoculated) and pathogen-induced gene expression in cacao pods from trees resistant and susceptible to MR. The greatest number of differentially expressed genes (DEGs) ( n = 2,039) was identified in susceptible material following inoculation with MR (7 days postinoculation), with the most common pathway categories being cell growth/death ( n = 102), signaling ( n = 308), and carbohydrate metabolism ( n = 141). Resistant material showed little overall change in gene expression (five DEGs) following pathogen inoculation, suggesting that infection had not become established. For this reason, differences in constitutive gene expression are likely to provide the most relevant information on FPR resistance in this study. In the absence of the pathogen, 144 genes were expressed at a higher level in the resistant material and 265 at a higher level in the susceptible material. The genes most highly upregulated in resistant material encode for disease resistance proteins in the leucine-rich repeat family and cysteine-rich receptor-like protein kinases. Ten DEGs were located within quantitative trait loci on chromosomes 2, 7, and 9 previously associated with FPR resistance in this population. This study provides the first analysis of constitutively expressed genes contributing to FPR resistance and identifies significant genes within known disease resistance quantitative trait loci. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .