Two new haliclonadiamine derivatives, halichondriamine C (1) and 1-epi-halichondriamine C (2), were isolated from the Okinawan marine sponge Haliclona sp. together with known haliclonadiamine (3) and papuamine (4). The structures of 1 and 2 were elucidated based on their spectroscopic data by comparisons with those for related compounds. Compounds 1 and 2 were epimers of each other at the C-1 position. Compounds 1–4 inhibited the growth of Mycobacterium smegmatis and M. bovis BCG and exhibited antibacterial activities against M. avium and M. intracellulare as pathogens of M. avium complex (MAC) disease. © 2018 Phytochemical Society of Europe