Sexual reproduction is critical to coral population dynamics and the long-term regeneration of coral reefs. Bleaching, disease, and/or anthropogenic-induced tissue/colony loss reduce reproductive output. This is the first attempt to explore the effect of a biotic disease on the reproduction of scleractinian corals. The study aimed to assess the effect of yellow band disease (YBD) on the reproduction of the important Caribbean reef-builder Montastraea faveolata. Tissue samples were collected from diseased, transition, and healthy-looking areas in each of 5 infected colonies and from 5 healthy controls in southwest Puerto Rico. The effect of disease-induced mortality was assessed by collecting samples from the edge and center of surviving small and large, healthy-looking tissue patches from large, previously infected tagged colonies. Fecundity was significantly lower in disease lesions compared to transition and healthy-looking tissues and the controls (99% fewer eggs). Fecundity in transition areas was significantly lower (50%) than in healthy-looking tissues in diseased colonies, which had 23% lower fecundity than control tissues. Although this fecundity drop was not statistically significant, it could indicate a systemic effect of YBD across the colony. Large and small patches had 64 and 84% fewer eggs than controls, respectively, and edge polyps had 97% fewer eggs than those in central control areas. Field observations of the spawning behavior of each tissue area corroborated the histological results. Our results indicate that YBD significantly compromises the reproductive output of M. faveolata, potentially reducing the fitness and consequently, the recovery of this important reef-building species on Caribbean coral reefs.