A species-rich, abundant marine invertebrate fauna inhabits the mouth of the Slough, the channels, mudflats and salt marshes. The upper or back-bay invertebrate fauna is dominated by infaunal species that brood their young. Several species of large infaunal clams are abundant along the main channel. The gaper clam and the Washington clam are most abundant at the Slough's mouth. Dense beds of rough paddock clam dominate the areas around Seal Bend and Moonglow Dairy.
Many polychaete worms live in both the intertidal zone and the subtidal channels.
The intertidal mudflats also harbor dense assemblages of small tube-dwelling and mobile invertebrates. There is a rich fish fauna in Elkhorn Slough, dominated by marine and estuarine species. The fish population peaks in both the Spring and Summer. The most common species are the staghorn sculpin, English sole, starry flounder and several species of perches. Leopard sharks, gray and brown smoothhound sharks and several species of rays also live in the Slough.