The “campo rupestre” is a montane vegetation mosaic associated with rocky outcrops, with outstanding levels of endemism. Hexasepalum Bartl. ex DC. is nested in the Spermacoceae, the largest predominantly herbaceous tribe in the Rubiaceae. This genus, with 14 accepted species, is distributed mostly in the Americas. Brazil is home to eight species, occurring mainly in the Caatinga and Cerrado (including the “campo rupestre”) domains. The analysis of specimens collected in the “campo rupestre” of Bahia (NE Brazil) and Minas Gerais (SE Brazil) has revealed that these are new to science. Hexasepalum bacigalupoae Cabaña Fader & E.L.Cabral sp. nov. is mostly similar to Hexasepalum apiculatum (Willd.) Delprete & J.H.Kirkbr., but differs by its 3–5-fimbriate stipular sheath (vs. 7–9fimbriate in H. apiculatum) and mericarps with flat ventral faces (vs. with two depressions). Hexasepalum motaviananum Cabaña Fader, J.A.M.Carmo & R.M. Salas sp. nov. is similar to Hexasepalum zappiae E.L.Cabral & Cabaña Fader, but differs by its ovate leaves (vs. linear leaves in H. zappiae), 6–7(8)-lobed calyx (vs. 4–5-lobed calyx), and the ventral surface of the seed with a “Y”-shaped groove, delimited by an apical fold, without apical grooves (vs. the ventral side of the seed without a Y-shaped groove nor apical fold, with 3–5 apical grooves). These new species are described and illustrated. We comment on their distribution, habitat, and taxonomy. We also provide an updated key to the species of Hexasepalum. Hexasepalum bacigalupoae and H. motaviananum are preliminarily assessed as Endangered and Critically Endangered, respectively, underscoring the crucial importance of conserving the “campo rupestre.”