Stony Brook Southampton Hospital, centrally located in the Village of Southampton, New York, is a 125-bed hospital accredited by the Joint Commission. A location of Stony Brook Medicine, Stony Brook Southampton Hospital is a New York State-designated Stroke Center and the home of the first Level III Trauma Center on the East End of Long Island. The hospital admits more than 6,000 patients annually and has about 25,000 emergency department visits each year (about 50% during the summer season). The hospital officially became part of the Stony Brook Medicine healthcare system on August 1, 2017.

In 1909, the Southampton Hospital Association bought the Hervey J. Topping house on the corner of Lewis Street and Meeting House Lane and planned to build the hospital on an adjoining lot. In 1911, Samuel Parrish donated 2.5 acres (1.0 ha) on Old Town Road, stretching from Meeting House Lane to Herrick Road, where the present hospital opened in 1913 and still stands today. The plans for the original hospital building were donated by society architect T. Markoe Robertson, and were designed to be able to grow. Over the next few decades, the original facility was expanded with several wings and off-site buildings, including the Parrish Memorial Hall, Schenck Memorial Building, and Todd Nursing Home.

The Audrey and Martin Gruss Heart & Stroke Center opened in 2015. As part of the hospital's merger with the Stony Brook Medicine health system, the Center gained a new cardiac catheterization laboratory, which is the first on South Fork.

The Phillips Family Cancer Center opened in 2019. The facility contains South Fork's first radiation oncology unit.

Southampton Hospital joined the Stony Brook Medicine health system in 2017, and was renamed Stony Brook Southampton Hospital.

Stony Brook Southampton Hospital became a Level III trauma center in May 2021.

In 2019, the Southampton Hospital Association announced a planned $305 million relocation of Southampton Hospital to 15 acres on the campus of Stony Brook Southampton . Rafael Viñoly Architects and HKS Architects were named to design the new campus. The project was originally anticipated to be completed by 2023, but has been delayed to 2025 due to the COVID-19 pandemic.

In August 2020, plans were announced to build a satellite East Hampton Emergency Department slated to cost between $35 million and $40 million. The facility received a $10 million state grant and the philanthropic campaign has raised another $38 million as of 2022. Perkins Eastman was selected to design the project, and construction began in May 2022. The facility is anticipated to open in Spring 2025.

The Southampton Hospital Foundation, a separate nonprofit corporation with an independent Board of Trustees, supports Stony Brook.

• Jacqueline Kennedy Onassis (1929–1994), First Lady of the United States. First First Lady to be born in a hospital.