Salinaphthoquinones A-E (<b>1</b>-<b>5</b>) were isolated from a marine <i>Salininispora arenicola</i> strain, recovered from sediments of the St. Peter and St. Paul Archipelago, Brazil. The structures of the compounds were elucidated using a combination of spectroscopic (NMR, IR, HRESIMS) data, including single-crystal X-ray diffraction analysis. A plausible biosynthetic pathway for <b>1</b>-<b>5</b> is proposed. Compounds <b>1</b> to <b>4</b> displayed moderate activity against <i>Staphylococcus aureus</i> and <i>Enterococcus faecalis</i> with MIC values of 125 to 16 μg/mL.