Chemical investigation of the mangrove endophytic fungus Cladosporium sp. SCNU-F0001 resulted in the isolation and identification of a new macrolide compound named thiocladospolide E (1) and a novel macrolide lactam named cladospamide A (2), along with the known cladospolide B (3). The structures were elucidated based on spectroscopic methods, and the absolute configurations were determined by X-ray diffraction and HPLC analysis after chemical derivatization. All compounds were tested for their antibacterial and cytotoxic activity.