Elkhorn Slough is a 7-mile-long (11 km) tidal slough and estuary on Monterey Bay in Monterey County, California. It is California's second largest estuary and the United States' first estuarine sanctuary. The community of Moss Landing and the Moss Landing Power Plant are located at the mouth of the slough on the bay. The Elkhorn Slough National Estuarine Research Reserve and Elkhorn Slough State Marine Conservation Area (SMCA) are in the area.

Elkhorn Slough harbors the largest tract of tidal salt marsh in California outside the San Francisco Bay and provides much-needed habitat for hundreds of species of plants and animals, including more than 340 species of birds. It has been designated as a protected Ramsar site since 2018.

The name of the slough derives from the native tule elk Cervus canadensis nannodes, now extirpated from the region.

Elkhorn Slough occupies the western reaches of Elkhorn Valley, a relic river valley eroded by drainage pouring out of the Santa Clara Valley and/or Great Valley of California (before the Golden Gate opened) into Monterey Bay during the early Pleistocene. In the mid-1850s A.D. Elkhorn Slough was a minor tributary to the much larger Pajaro-Salinas River system which shared a common entrance to the Pacific Ocean north of Moss Landing. In 1909 winter storms modified the course of the Salinas River to its present location south of Moss Landing, while Elkhorn Slough persisted as a tributary to the Old Salinas River channel. Construction of jetties at the Moss Landing Harbor in 1946 provided a direct link between the Pacific Ocean and Elkhorn Slough. At this time, salt marshes began to retreat from the axis of Elkhorn Slough as it evolved into its present form as a relatively stable estuarine embayment.

Carneros Creek is the primary source of freshwater flowing into Elkhorn Slough. McClusky Slough to the north and Moro Cojo Slough to the south also provide freshwater inputs.

Elkhorn Slough, one of the largest estuaries in California, provides essential habitat for over 700 species, including aquatic mammals, birds, fish, invertebrates, algae and plants. The slough area is home to California's greatest concentration of sea otters, as well as populations of endangered Santa Cruz long-toed salamander and the threatened California red-legged frog. The population of sea otter living in Elkhorn Slough reflect that the species is well-adapted for estuarine habitat, and may be a model for the historical sea otter populations now extinct in San Francisco Bay.

Elkhorn Slough hosts year-round residents tightly associated with estuaries, such as pickleweed, eelgrass, oysters, gaper clams, and longjaw mudsuckers, as well as important seasonal visitors such as migratory shorebirds, sea otters, and sharks and rays. Habitat types include mudflats, tidal creeks and channels. Other vegetative species include such wildflowers as yellow mariposa lily, Calochortus luteus.

Conservation groups have worked to remedy indirect harm from human activity in the region in addition to preventing direct damage to the ecosystem by harvest of resources and conversion of land.