Fungi in the Botryosphaeriales (Ascomycetes) are common endophytes in woody plants with a wide global distribution and in some cases they are important tree pathogens. The aim of this study was to consider the possible cause of die-back on native coastal red milkwood (Mimusops caffra) trees growing on the east coast of South Africa. Samples were taken from symptomatic tissue and isolations were made. The resulting isolates were identified based on DNA sequence data from the rDNA-ITS, translation elongation factor 1-α and β-tubulin loci. Two new species in the Botryosphaeriales, namely Neofusicoccum variabile sp. nov. and Pseudofusicoccum africanum sp. nov., were found together with an isolate of N. mangroviorum. Neofusicoccum mangroviorum produced significantly longer lesions than the other two species and the control inoculations in pathogenicity tests and it appears to be the cause of the die-back disease.