Seed dispersal is a fundamental process that is highly threatened by the rapid decline of large-bodied frugivores worldwide. The Brazilian Cerrado, the largest savanna in the world, represents an ideal site for investigating seed dispersal because of its biodiversity, environmental challenges, and knowledge shortfalls. We performed a systematic literature review to analyze the seed dispersal network in the Cerrado and the potential impacts of the defaunation of large-bodied frugivores on it. We considered network metrics, calculated the defaunation index of the frugivore assemblage, and compared traits among different fruit-sized plants and their respective dispersers in the network. We retrieved 1565 interactions involving 193 plant species and 270 animal species. Results show that the Cerrado seed dispersal network is slightly nested and considerably modular, dominated by small- to medium-sized generalist species, such as passerines, marsupials, and mesocarnivores. Nonetheless, large-bodied frugivores like the lowland tapir have a key role in the network due to their great foraging and network integration capacity. The Cerrado frugivore assemblage is moderately defaunated, with possible effects in its interactions with large-fruited plants. The Cerrado's defaunation and functional loss of large vertebrates deserve urgent attention to further understand the impacts on seed dispersal mechanisms and ecosystem functioning.