Plant communities of South Slough saltmarshes are typical of the region, and include tufted hairgrass, saltgrass, pickleweed, Baltic rush, jaumea and Lyngby's sedge. A few small marshes in the South Slough support the less common salt marsh bird's beak and sea lavender. These eelgrass beds, together with the deep channels in the estuary, shelter a large number of fish and invertebrates. The Reserve maintains resident populations of herons, osprey, gulls and eagles. In addition, the estuary is a foraging and resting area for brown pelicans, and a major stop on the coastal flyway for migratory birds.
Uplands provide feeding and nesting sites for a number of raptors such as the red-tailed hawk.
Audubon Christmas counts in the estuary have identified over 21,000 individual birds of 89 species each December. Harbor seals and sea lions feed in the estuary year round. An additional ten thousand harbor seals, elephant seals, Steller sea lions and California sea lions visit offshore areas annually, with many finding their way into the estuary to feed. The Reserve uplands support deer, elk, bear, porcupine, bobcat, skunks and coyote. Freshwater ponds, wetlands and marshes support beavers.