<jats:title>Abstract</jats:title><jats:p>Two new tricyclic sesterterpenes, fusaprolifins A and B (<jats:bold>1</jats:bold> and <jats:bold>2</jats:bold>), and three new 2<jats:italic>H‐</jats:italic>pyran‐2‐one derivatives, prolipyrones A – C (<jats:bold>3</jats:bold>–<jats:bold>5</jats:bold>), were isolated and characterized from <jats:italic>Fusarium proliferatum</jats:italic> MA‐84, an endophytic fungus obtained from the fresh tissue of the marine mangrove plant <jats:italic>Bruguiera sexangula.</jats:italic> In addition, two known sesterterpenes, terpestacin (<jats:bold>6</jats:bold>) and fusaproliferin (<jats:bold>7</jats:bold>), and one known 2<jats:italic>H</jats:italic>‐pyran‐2‐one derivative, gibepyrone D (<jats:bold>8</jats:bold>), were also identified. The structures of these compounds were elucidated by detailed spectroscopic analyses. Fusaprolifin A (<jats:bold>1</jats:bold>) showed moderate activity against brine shrimp (<jats:italic>Artemia salina</jats:italic>), with a lethality rate of 49.5% at 100 μg/ml, while fusaprolifin B (<jats:bold>2</jats:bold>) showed weak activity.